Patient Information Leaflet: Information for the Patient

Alprazolam Combix 0.25 mg Tablets EFG

Read this leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
  If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Alprazolam Combix is and what it is used for

2. What you need to know before you start taking Alprazolam Combix

3. How to take Alprazolam Combix

4. Possible side effects

5. Storage of Alprazolam Combix

6. Contents of the pack and additional information

Alprazolambelongs to a group of medications called benzodiazepine tranquilizers (anxiolytics).

It is indicated for the treatment of:

-Generalized anxiety disorder and anxiety associated with depressive symptoms.

-Panic disorders with or without agoraphobia (fear of places where it may be difficult or embarrassing to escape or obtain help).

Benzodiazepines are only indicated for the treatment of a severe disorder that limits the patient's activity or subjects them to extreme stress.

Benzodiazepines should not be used alone for the treatment of anxiety associated with depression. Alprazolam is not recommended for the treatment of depression.

Do not take Alprazolam Combix

-if you are allergic to alprazolam, benzodiazepines, or any of the other components of this medication (listed in section 6)

-if you have respiratory difficulties related or unrelated to sleep (sleep apnea)

-if you have a condition called myasthenia gravis, characterized by muscle weakness

-if you have severe liver damage

Warnings and precautions

Consult your doctor or pharmacist before starting to take Alprazolam Combix

-if you have any lung, kidney, or liver problems

-if you have felt or feel so depressed that you have had thoughts or ideas of suicide

-after prolonged use of alprazolam, tolerance may develop (see section “If you stop taking Alprazolam Combix”)

-there is a risk of developing addiction/dependence when using alprazolam

-if during treatment you notice symptoms of mania (state of overexcitement, feeling of euphoria, or hyperirritability) or hypomania (state of excitement and excessive activity)

-the treatment with benzodiazepines, including alprazolam, may cause dependence, 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 only be under medical prescription (never because they have worked in other patients) and should never be recommended to others

-do not increase the prescribed doses, nor prolong the treatment longer than recommended

-consult your doctor regularly so that they can decide if you should continue with the treatment

-do not combine several benzodiazepines regardless of their indication

-when stopping treatment with alprazolam, rebound-like symptoms may appear (see section “If you stop taking Alprazolam Combix”). To avoid this, it is recommended not to stop treatment abruptly, but to gradually reduce the dose, as instructed by your doctor

-the use of alprazolam with opioid-type medications may cause deep sedation, respiratory depression, coma, and death

-benzodiazepines may cause memory loss and reactions such as:

anxiety, agitation, irritability, aggression, delirium, anger attacks, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse effects on behavior. If this occurs, discontinue treatment and consult your doctor

-it is very important to inform your doctor if you have a history of drug and alcohol consumption

Other medications and Alprazolam Combix

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

Alprazolam may interact with other medications. Inform your doctor or pharmacist if you are taking any of the following medications:

-Central nervous system depressants, as they may potentiate the sedative effect of alprazolam:

-Major tranquilizers (antipsychotics)

-Sleep inducers (hypnotics)

-Medications used to treat depression

-Medications used to treat epilepsy (antiepileptics)

-Opioid analgesics and narcotics (morphine derivatives), as they may increase the feeling of euphoria, leading to increased psychological dependence

-Medications used to treat anxiety (anxiolytics/sedatives)

-Anesthetics

-Antihistamines (allergy medications) sedatives

-The concomitant use of alprazolam and opioids (powerful analgesics, medication for opioid addiction treatment, and some cough medications) increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and may be potentially fatal. Therefore, concomitant use should only be considered when other treatment options are not possible

-However, if your doctor prescribes alprazolam along with opioids, the dose and duration of concomitant treatment should be limited by your doctor

-Inform your doctor about all the opioid medications you are taking and follow your doctor's dosage recommendations closely. It may be helpful to inform friends or family members to be aware of the signs and symptoms mentioned above. Contact your doctor if you experience any of these symptoms

-There are some groups of medications that, due to their action in the body (inhibitors of cytochrome P450), may interact with alprazolam and, in some cases, increase its activity. Some of the medications that may interact with alprazolam are:

-Medications used to treat fungal infections such as ketoconazole, itraconazole, posaconazole, or voriconazole. It is not recommended to take them at the same time as alprazolam

-The following antidepressants: nefazodone, fluvoxamine, and fluoxetine

-Protective gastric medications such as cimetidine

-Dextropropoxyphene (narcotic analgesic)

-Oral contraceptives

-Diltiazem (anti-hypertensive)

-Macrolide antibiotics such as erythromycin, troleandomycin, clarithromycin, and telithromycin

-Medications used to treat AIDS such as ritonavir, etc.

-Digoxin (medication used to suppress or prevent heart rhythm alterations)

Taking Alprazolam Combix with food, drinks, and alcohol

Avoid drinking alcoholic beverages during treatment. The effect of alcohol may potentiate sedation, and this may affect your alertness (see section “Driving and operating machinery”)

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

Alprazolam is not recommended during pregnancy or breastfeeding, unless, in the doctor's opinion, the benefits outweigh the risks for the baby

If, at the doctor's discretion, alprazolam is administered during a late stage of pregnancy or during delivery, the following effects may occur in the newborn: decreased body temperature (hypothermia), decreased muscle tone (hypotonia), and moderate respiratory depression

Newborns born to mothers who take benzodiazepines chronically during the last period of pregnancy may develop physical dependence, which may trigger withdrawal syndrome in the postnatal period

Use in children and adolescents (under 18 years)

Alprazolam is not recommended for children and adolescents under 18 years. Benzodiazepines should not be administered to children unless it is strictly necessary and prescribed by a doctor. The efficacy and safety of alprazolam in children under 18 years have not been established

Use in elderly patients (over 65 years)

Alprazolam may affect this group of patients more than young patients. If you belong to this group, your doctor may reduce the dose and monitor your response to treatment. Please follow their instructions carefully (see section “How to take Alprazolam Combix”)

Benzodiazepines and related products should be used with caution in elderly patients, due to the risk of sedation and/or muscle weakness that may cause falls, often with serious consequences in this population

Special patient groups

If your liver or kidneys do not function well, consult your doctor, who may advise you to use a lower dose of alprazolam

If you have respiratory problems, inform your doctor

Driving and operating machinery

Alprazolam may affect your ability to drive or operate machinery, as it may cause drowsiness, decrease your attention, or decrease your reaction time. These effects are more likely to occur at the beginning of treatment or when the dose is increased. Do not drive or operate machinery if you experience any of these effects

These effects may be potentiated if you consume alcohol at the same time

Alprazolam Combix contains lactose monohydrate and sodium benzoate (E-211)

If your doctor has told you that you have an intolerance to certain sugars, consult them before taking this medication

This medication contains 0.15 mg of sodium benzoate (E-211) in each tablet

If you need additional information on this point, consult your doctor or pharmacist

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

Dosage:

The tablet or its part will be ingested without chewing, with the help of a little liquid. Your doctor will prescribe the alprazolam presentation most suitable for you, according to the dose you need.

The recommended dose is:

-For the treatment of anxiety states and anxiety associated with depression symptoms:states of anxiety and anxiety associated with depression symptoms:

- The initial dose is 0.25 mg to 0.5 mg of alprazolam three times a day.

- The usual dose ranges from 0.5 mg to a maximum of 4 mg per day, divided into 3 or 4 doses.

-For the treatment of anxiety disorders:anxiety disorders:

- A recommended initial dose of 0.5 mg to 1 mg of alprazolam at bedtime is recommended.

- Your doctor will then adjust the dose according to your response to treatment. Dose adjustments should be made by increasing the dose by no more than 1 mg every 3 or 4 days. Additional doses may be added to reach the posological scheme of 3 or 4 times a day.

In elderly patients, with chronic respiratory insufficiency, liver or kidney impairment, the initial recommended dose is 0.25 mg of alprazolam, 2 or 3 times a day, with the amount of alprazolam ingested per day ranging from 0.5 mg to 0.75 mg in divided doses, which can be gradually increased as needed and well tolerated.

No individual dose should exceed the indicated limits, and the total daily dose should not either, unless your doctor indicates otherwise.

Duration and discontinuation of treatment:

The duration of treatment should be as short as possible (should not exceed 12 weeks, including the withdrawal period from treatment). If your doctor considers it necessary to prolong treatment in your case, they will do so for limited periods and will closely monitor your situation.

You should never interrupt treatment abruptly. Your doctor will indicate the duration of treatment depending on the evolution of your disease and will explain how to gradually reduce the dose until you complete your treatment.

If you estimate that the action of alprazolam is too strong or too weak, inform your doctor or pharmacist.

If you take more Alprazolam Combix than you should

If you have taken more alprazolam than you should, consult your doctor or pharmacist immediately or go to the nearest hospital with this leaflet.

Benzodiazepine overdose generally manifests by different degrees of depression of the central nervous system, ranging from somnolence to coma. Symptoms include somnolence (drowsiness), speech disorders (dysarthria), coordination disorders, confusion, lethargy (a state of deep and prolonged somnolence), muscle tone decrease (hypotonia), decreased blood pressure, respiratory depression, rarely coma, and very rarely death. Serious sequelae are rare, unless alprazolam is taken with other medications or alcohol.

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

If you forgot to take Alprazolam Combix

Do not take a double dose to compensate for the missed doses. If the missed dose is recent, take your dose immediately, and if not, wait for the next dose without taking a double dose to compensate.

If you interrupt treatment with Alprazolam Combix

Alprazolam treatment can cause dependence, so when stopping alprazolam administration abruptly, withdrawal symptoms may appear.

The withdrawal symptoms that may occur are: headache, muscle pain, anxiety, tension, restlessness, confusion, irritability, general feeling of discontent (dysphoria), insomnia, intolerance to light, sounds, and physical contact, paresthesias and cramps in the extremities and abdomen, vomiting, sweating, tremors, depersonalization, hallucinations, and convulsions. If this occurs, you should consult your doctor immediately.

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

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

The side effects that may occur during treatment with alprazolam predominantly occur at the beginning of treatment and generally disappear with continued administration or after a reduction in dose.

Very common side effects(may affect more than 1 in 10 people):

- Depression.

-Sedation, drowsiness, coordination disorder (ataxia), memory alteration, difficulty articulating words (dysarthria), dizziness, headache.

- Constipation, dry mouth.

- Fatigue, irritability.

Common side effects(may affect up to 1 in 10 people):

-Sensation of confusion, disorientation, alteration of sexual desire (libido), anxiety, difficulty sleeping (insomnia), nervousness.

- Abnormal coordination, balance alteration, difficulty concentrating, excessive sleep (hypersomnia), deep and prolonged somnolence (lethargy), tremor.

- Nausea, decreased appetite.

- Blurred vision.

- Dermatitis.

- Sexual dysfunction.

- Weight changes.

Uncommon side effects(may affect up to 1 in 100 people):

-Mental and behavioral disorders (mania), hallucinations, anger reactions, agitation, dependence.

- Memory loss (amnesia).

-Loss of muscle strength.

-Inability to retain urine in the bladder (urinary incontinence).

-Irregular menstruation.

-Withdrawal symptoms.

Frequency not known(cannot be estimated from available data):

-Increased levels of prolactin in the blood (hormone responsible for stimulating and maintaining lactation after childbirth).

-Mental and behavioral disorders (hypomania), aggression, hostility, abnormal thinking, psychomotor hyperactivity, drug abuse.

-Autonomic nervous system imbalance, involuntary muscle contractions (dystonia).

-Gastrointestinal disorder, hepatitis, liver function alteration, yellowing of the skin and white of the eyes (jaundice).

-Peripheral edema.

-Angioedema (swelling under the skin's surface).

-Phototoxicity (exaggerated response to light).

-Urinary retention in the bladder.

-Increased intraocular pressure.

With the use of benzodiazepines, the following may occur:

-Somnolence, lack of reaction to emotional stimuli (emotional numbing), reduced state of alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, or double vision. These phenomena occur predominantly at the beginning of treatment and generally disappear with continued administration. Occasionally, gastrointestinal alterations, changes in sexual desire, or skin reactions may occur.

-A loss of memory (amnesia) may develop, which may be associated with inappropriate behavior.

-The use of benzodiazepines may unmask an existing depression.

-When using benzodiazepines or similar compounds, reactions such as restlessness, agitation, irritability, aggression, delirium, anger attacks, nightmares, hallucinations, psychosis, inappropriate behavior, and other conduct alterations may occur. These reactions can be severe and occur more frequently in children and the elderly.

-The administration of the product (even at usual doses) may lead to the development of physical dependence. Discontinuation of treatment may lead to the development of withdrawal or rebound phenomena. Psychological dependence may occur. Cases of abuse have been reported.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Usehttps://www.notificaram.es. By reporting side 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.

This medication does not require special storage conditions.

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 trash. Dispose of packaging and unused medications at the SIGRE collection point at the 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 Alprazolam Combix 0.25 mg tablets EFG

-The active ingredient is alprazolam, each tablet contains 0.25 mg.

-The other components are: lactose monohydrate, microcrystalline cellulose, pregelatinized cornstarch, sodium docusate, sodium benzoate (E-211), anhydrous colloidal silica, magnesium stearate, and yellow PB-22877 dye (compound of lactose monohydrate and quinoline yellow (E-104)).

Appearance of the product and contents of the packaging

Alprazolam Combix 0.25 mg are yellow, biconvex, round, and scored on one side, uncoated tablets.

The tablets are presented inPVC-Aluminumblister packs in boxes of 30 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

Bluepharma - Indústria Farmacêutica, S.A.

S. Martinho do Bispo

3045-016 Coimbra

Portugal

Last review date of this leaflet: February 2022

The detailed and updated information on this medication is available on the website of theSpanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/