FRONTAL

Package leaflet: Information for the user

FRONTAL 0,25 mg tablets, 0,50 mg tablets, 1 mg tablets, 0,75 mg/ml oral drops, solution

Alprazolam
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What FRONTAL is and what it is used for
2. What you need to know before taking FRONTAL
3. How to take FRONTAL
4. Possible side effects
5. How to store FRONTAL
6. Contents of the pack and other information

1. What FRONTAL is and what it is used for

FRONTAL contains the active substance alprazolam. Alprazolam belongs to a group of medicines called benzodiazepines (anxiolytic medicines).
FRONTAL is used in adult patients for the treatment of anxiety symptoms when the disorder is severe, disabling, or causes the individual severe distress. This medicine is indicated only for short-term use.

2. What you need to know before taking FRONTAL

Do not take FRONTAL

• if you are allergic to alprazolam, benzodiazepines, or any of the other ingredients of this medicine (listed in section 6);
• if you have myasthenia gravis, a disease causing severe muscle weakness;
• if you have severe breathing problems (respiratory failure);
• if you have severe liver problems (hepatic failure);
• if you have breathing difficulties during sleep ( sleep apnea );
• if you suffer from an eye condition called acute angle-closure glaucoma, a problem caused by increased pressure inside the eyes;
• during the first 3 months of pregnancy and if you are breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
This medicine may reduce or even abolish consciousness, may cause a significant reduction in spontaneous breathing ability, coma, and death if taken together with other medicines acting on the brain and mind (e.g. opioids, antipsychotics, hypnotics-sedatives) (see section “Other medicines and FRONTAL”).
Talk to your doctor or pharmacist before taking FRONTAL if:

• you are elderly and/or debilitated. Your doctor will prescribe a reduced dose of this medicine; remember to use this medicine with caution as it may cause sedation and/or musculoskeletal weakness, increasing your risk of falls, often with serious consequences;
• you have chronic breathing problems (chronic respiratory insufficiency), as this medicine may worsen your condition;
• you have kidney problems (renal failure) or liver problems of mild to moderate degree (mild to moderate hepatic insufficiency);
• you suffer from severe depression. FRONTAL, like other benzodiazepines, should not be used alone to treat depression or anxiety associated with depression, as it may worsen suicidal tendencies and cause mood changes;
• you suffer from psychosis, a serious mental illness altering behavior and causing difficulties in social interactions. FRONTAL is not recommended as primary treatment for this condition;
• you are being treated with other medicines acting on the brain and mind, as FRONTAL may enhance the effects of these medicines (see section “Other medicines and FRONTAL”);
• you have or have previously had problems with abuse and dependence on alcohol, drugs, or other medicines, as the risk of developing dependence on FRONTAL is higher (see section “Development of dependence”);
• you suffer from rare hereditary problems of intolerance to a particular sugar (galactose).

Memory disturbances
A few hours after taking FRONTAL, you may experience difficulty remembering events that occurred after taking the medicine.

Paradoxical reactions
FRONTAL may cause effects opposite to those expected ( paradoxical effects ) (see section 4 “Possible side effects”). These effects are more common in children and elderly patients. If you experience such effects, consult your doctor, as treatment with FRONTAL should be discontinued.

Development of tolerance
After several weeks of treatment, a decrease in the effectiveness of FRONTAL may occur.

Development of dependence
FRONTAL causes dependence (i.e. you may feel an increasing desire to take the medicine or may develop physical symptoms that diminish or disappear only after taking the medicine). The likelihood of developing dependence increases with higher doses and longer duration of treatment. Therefore, your doctor will prescribe the most appropriate treatment based on your condition, using the lowest effective dose for the shortest possible duration. Your doctor will also advise you when to attend follow-up visits to monitor your health during FRONTAL therapy.

Incorrect use of FRONTAL
You must take this medicine ONLY if prescribed by a doctor and purchased from a pharmacy.
Some people tend to abuse FRONTAL and other similar medicines known as benzodiazepines.
Moreover, some individuals obtain these medicines illegally (e.g. black market, internet, friends, family, etc.), sometimes with the intent of reselling them. DO NOT take FRONTAL if this medicine has not been prescribed to you by a doctor. DO NOT take FRONTAL if you are unsure whether this medicine was purchased from a pharmacy.

Children and adolescents
The efficacy and safety of FRONTAL in children and adolescents under 18 years of age have not been established. Your doctor will decide whether FRONTAL can be administered to children and adolescents based on their individual conditions.

Other medicines and FRONTAL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Concomitant use of FRONTAL and opioids (strong analgesics, medicines for addiction treatment, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be life-threatening. Therefore, concomitant use should only be considered when no other treatment options are available.
However, if your doctor prescribes FRONTAL together with opioids, the dose and duration of concomitant treatment must be limited by the doctor.
Inform your doctor about all opioid medicines you are taking and carefully follow the doctor’s dosage recommendations. It may be helpful to inform family members or friends to watch for the signs and symptoms listed above.
Contact your doctor if you experience such symptoms.
Caution is required when FRONTAL is taken together with the following medicines:

• medicines acting on the brain and mind * such as:
  o antipsychotics, medicines for treating certain mental illnesses;
  o hypnotics, sleep-inducing medicines;
  o sedatives, tranquillizers;
  o anxiolytics, medicines for treating anxiety;
  o antidepressants (e.g. nefazodone, fluvoxamine, fluoxetine, imipramine, desipramine), medicines for treating depression;
  o narcotic analgesics, opioids, medicines for treating severe pain;
  o antiepileptics, medicines for treating epileptic seizures;
  o anesthetics. Anesthetics, when administered together with FRONTAL, may cause euphoria, increasing the likelihood of developing dependence on FRONTAL;
  o sedating antihistamines, medicines for treating allergic symptoms;
  * If you take FRONTAL together with one or more of these medicines or together with alcoholic beverages, these substances may contribute to reduced brain and mental function, potentially leading to reduced spontaneous breathing, coma, and death (see section Warnings and precautions).
• analgesics and cough suppressants containing opium or its derivatives. These medicines, like FRONTAL, reduce spontaneous breathing ability;
• cimetidine, a medicine used to reduce stomach acidity;
• propoxyphene, a medicine used for pain relief;
• oral contraceptives;
• diltiazem, a medicine used to lower blood pressure;
• digoxin (a medicine used to increase the force of heart contraction). If you are elderly, taking FRONTAL may increase the likelihood of developing digoxin-related toxic effects.

The following medicines may increase the effects of FRONTAL:

• ketoconazole, itraconazole, posaconazole, and voriconazole, medicines used to treat fungal infections;
• erythromycin, clarithromycin, telithromycin, and troleandomycin (antibiotics);
• protease inhibitors (e.g. ritonavir), medicines used to treat HIV infection. If you are being treated with protease inhibitors, your doctor may advise discontinuing FRONTAL treatment due to interaction with these medicines.

FRONTAL and alcohol
Do NOT drink alcohol while taking FRONTAL, as alcohol enhances the effects of this medicine.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
This medicine must not be taken during the first 3 months of pregnancy as it may cause congenital malformations in the fetus. Your doctor will assess whether you can take this medicine during the second and third trimesters of pregnancy.
If you take this medicine during the last months of pregnancy or during labor, the newborn may show the following symptoms:

• poor muscle tone (axial hypotonia);
• breathing difficulties (respiratory depression or apnea) and difficulty feeding;
• low body temperature (hypothermia);
• withdrawal symptoms (see section 3 “If you stop taking FRONTAL”). These effects are reversible and may last from several days up to 1–3 weeks after birth.

Breastfeeding
Do NOT breastfeed while taking FRONTAL, as this medicine passes into breast milk.

Driving and using machines
Do NOT drive or operate machinery if, during treatment with FRONTAL, you experience loss of concentration or muscle control, or feel drowsy or dizzy. These effects may be intensified if you have not slept enough or have consumed alcoholic beverages.

FRONTAL tablets contain lactose and sunset yellow (E110)
The 0.25 mg, 0.50 mg, and 1 mg FRONTAL tablets contain lactose, a type of sugar. If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.
The 0.50 mg FRONTAL tablets contain the colorant sunset yellow (E110), which may cause allergic reactions.

FRONTAL oral drops, solution contains ethanol and propylene glycol
This medicine contains 16 vol% ethanol (alcohol), e.g. up to 172 mg per dose, equivalent to 4 ml of beer or 2 ml of wine per dose.
It may be harmful for alcoholics.
This should be considered in pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.
This medicine contains 467 mg of propylene glycol per 20 drops (equivalent to 700 mg/ml).
If the child is under 5 years of age, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.
If you are pregnant or breastfeeding, do not take this medicine unless otherwise recommended by your doctor. Your doctor may perform additional monitoring during treatment.
If you suffer from liver or kidney disease, do not take this medicine unless otherwise recommended by your doctor. Your doctor may perform additional monitoring during treatment.

FRONTAL contains sodium
The 0.25 mg, 0.50 mg, 1 mg tablets and FRONTAL oral drops contain less than 1 mmol (23 mg) of sodium per dose, i.e., essentially ‘sodium-free’.

3. How to take FRONTAL

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor.

• Treatment of anxiety The recommended starting dose is 0.25 to 0.50 mg three times a day. If you prefer the drops formulation, the recommended starting dose is 10 to 20 drops three times a day. The dose may be gradually increased up to a maximum of 4 mg per day, divided into several doses. You should first increase the evening dose, followed by the daytime doses.

If you are elderly, have liver or kidney problems and/or are debilitated
The recommended starting dose is 0.25 mg (equivalent to 10 drops) 2–3 times a day.
Treatment with FRONTAL should last for the shortest time possible.
The maximum duration of treatment should not exceed 2–4 weeks. Prolonged treatment is not recommended. Your doctor will decide whether treatment may continue beyond the recommended maximum period.

Instructions for opening the dropper bottle

• Press down on the plastic cap and at the same time unscrew it.

• To close, screw the cap on tightly.

If you take more FRONTAL than you should
If you have taken an excessive dose of FRONTAL, contact your doctor immediately or go to the nearest Emergency Room.

• In milder cases, symptoms may include: mental confusion, drowsiness, difficulty speaking;
• In more severe cases, symptoms may include: loss of coordination, reduced muscle tone, low blood pressure, breathing difficulties, coma, death.

If you forget to take FRONTAL
If you forget to take a dose, take it as soon as you remember, unless it is almost time for your next dose. Do not take a double dose to make up for the forgotten dose.

If you stop taking FRONTAL
Do not stop taking FRONTAL suddenly. Always consult your doctor before stopping FRONTAL. You must gradually reduce the dose to avoid experiencing:

• Withdrawal symptoms such as: severe symptoms: feeling detached from oneself or the external world, numbness and tingling in arms or legs, increased sensitivity to light, sound and physical contact, hallucinations, epileptic seizures, muscle and abdominal cramps, vomiting, sweating, tremors, convulsions; or other symptoms: headache, muscle pain, anxiety, tension, restlessness, confusion, irritability, mild depression, insomnia;
• Rebound symptoms, for example anxiety. These symptoms are the same ones for which FRONTAL treatment was prescribed, and may temporarily reappear more intensely after abrupt discontinuation of treatment.

If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact your doctor immediately if you experience any of the following side effects, as treatment with FRONTAL must be discontinued:

• Effects opposite to those expected (paradoxical effects) (see section 2, "Paradoxical disorders"), such as:
  • restlessness
  • agitation
  • irritability
  • aggressiveness
  • feelings of disappointment
  • anger
  • nightmares
  • hallucinations
  • disturbances in thinking
  • changes in behaviour

Contact your doctor immediately if you experience any of the following side effects, as they may be serious:

• swelling of the face, tongue, and throat, causing difficulty in swallowing and breathing (angioedema);
• difficulty in remembering events following administration of the medicine (see section 2, "Memory disturbances");
• unmasking of pre-existing depression;
• dependence (see section 2, "Development of dependence");
• withdrawal symptoms and rebound symptoms (see section 3, "If you stop taking FRONTAL").

Contact your doctor if you experience any of the following side effects:
Very common (may affect more than 1 in 10 people)

• depression
• sedation
• drowsiness
• loss of ability to coordinate movements
• memory disturbances
• difficulty speaking
• dizziness
• headache
• constipation
• dry mouth due to lack of saliva
• fatigue
• irritability

Common (may affect up to 1 in 10 people)

• decreased appetite, decreased or increased body weight
• confusion, disorientation
• increased or decreased sexual desire, sexual dysfunction
• anxiety
• insomnia, excessive sleepiness
• nervousness
• loss of balance, problems with coordination of movements
• loss of attention and concentration
• excessive drowsiness (lethargy)
• tremors
• vertigo
• slurred speech
• blurred vision
• nausea
• dermatitis

Uncommon (may affect up to 1 in 100 people)

• obsessive thoughts and behaviours
• inability to remember recent life events
• hallucinations
• agitation
• anger
• vomiting
• muscle weakness
• incontinence
• irregular menstrual cycle
• drug dependence
• drug withdrawal syndrome

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

• increased levels of prolactin (a natural hormone) in the blood
• mood changes
• hostile behaviour, abnormal thoughts
• aggressiveness
• impulsiveness and motor hyperactivity
• disturbances of the nervous system controlling involuntary bodily functions (e.g. internal organs and glands)
• involuntary muscle contractions causing unnatural postures
• stomach and intestinal disorders
• inflammatory liver diseases (hepatitis)
• altered liver function
• yellow/yellowish discoloration of the skin and mucous membranes (jaundice)
• skin reactions due to exposure to sunlight
• angioedema
• inability to completely empty the bladder
• swelling of the hands and feet due to fluid retention
• increased intraocular pressure
• abuse of this medicine (tendency to excessive or inappropriate use of FRONTAL)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting side effects helps provide more information on the safety of this medicine.

5. How to store FRONTAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
Tablets
Store in the original packaging to protect the medicine from light.
Drops
Validity after first opening: 90 days. Any excess medicine must be discarded. You may record the date of first opening in the designated space on the carton.
Store in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What FRONTAL contains
The active substance is alprazolam.
Tablets
One 0.25 mg FRONTAL tablet contains 0.25 mg of alprazolam.
The other components are lactose, microcrystalline cellulose, sodium docusate, colloidal silicon dioxide, maize starch, magnesium stearate.
One 0.50 mg FRONTAL tablet contains 0.50 mg of alprazolam.
The other components are lactose, microcrystalline cellulose, sodium docusate, colloidal silicon dioxide, maize starch, magnesium stearate, sunset yellow (E110).
One 1 mg FRONTAL tablet contains 1 mg of alprazolam.
The other components are lactose, microcrystalline cellulose, sodium docusate, colloidal silicon dioxide, maize starch, magnesium stearate, indigo carmine (E132).
Oral drops, solution
1 ml of FRONTAL oral drops solution contains 0.75 mg of alprazolam.
The other components are ethanol, propylene glycol, sodium saccharin, grapefruit flavour, purified water.

Description of the appearance of FRONTAL and contents of the pack
0.25 mg tablets: blisters of 20 and 30 white, shiny oval tablets with a smooth surface, marked with a score line on one side and "F" on the other.
0.50 mg tablets: blisters of 20 and 30 orange, shiny oval tablets with a smooth surface, marked with a score line on one side and "F" on the other.
1 mg tablets: blister pack of 20 blue, shiny oval tablets with a smooth surface, marked with a score line on one side and "F" on the other.
Oral drops, solution: 20 ml and 30 ml bottles containing a clear, colourless solution.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Aurobindo Pharma (Italia) S.r.l.
Via San Giuseppe, 102
21047 – Saronno (VA)
Italy

Manufacturer
Tablets
ICE S.p.A., Cantone Moretti, 29, 10015 (TO) – Ivrea – Italy
Doppel Farmaceutici S.p.A. - Via Volturno, 48 - Quinto de’ Stampi - 20089 Rozzano (MI)
Italy

Oral drops, solution
ICE S.p.A.
Cantone Moretti, 29
10015 (TO) – Ivrea – Italy