Gamibetal Complex

Patient Information Leaflet

Gamibetal Complex tablets

buxamina + phenobarbital + sodium phenytoin
Please read this leaflet carefully before using 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, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Gamibetal Complex is and what it is used for
2. What you need to know before taking Gamibetal Complex
3. How to take Gamibetal Complex
4. Possible side effects
5. How to store Gamibetal Complex
6. Package contents and other information

1. What Gamibetal Complex is and what it is used for

Gamibetal Complex contains buxamine and phenytoin, which belong to a group of medicines known as “antiepileptics” or “anticonvulsants”, and phenobarbital, which belongs to a group of medicines known as “barbiturates”.
This medicine is used for the treatment:

• of epilepsy;
• of convulsions in children.
  Consult your doctor if you do not feel better or if you feel worse.

2. What you need to know before using Gamibetal Complex

Do not use Gamibetal Complex

• if you are allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6);
• if you have a blood disorder called porphyria;
• if you have liver problems (hepatic insufficiency);
• if you have kidney problems (renal insufficiency);
• if you have bronchial or lung problems (respiratory insufficiency).

Warnings and precautions
Talk to your doctor or pharmacist before using Gamibetal Complex.
In some cases, patients treated with antiepileptic medicines may experience suicidal thoughts. If such thoughts occur, contact your doctor immediately.
Do not abruptly stop treatment with this medicine without first discussing it with your doctor, as this may cause sudden onset of epileptic seizures.
Exercise particular caution if:

• you have a predisposition to barbiturate dependence. This medicine contains phenobarbital, a barbiturate, which may lead to dependence;
• you are taking painkillers (analgesics);
• you are debilitated;
• you have a lung disease;
• you are scheduled for a metyrapone test or a protein-bound iodine test, inform your doctor who prescribed the test that you are taking Gamibetal Complex. The phenytoin contained in this medicine may alter the results of certain tests;
• you notice swellings in the neck (enlargement of lymph nodes) or develop a skin rash accompanied by redness, peeling, or blisters on the skin, consult your doctor immediately for discontinuation of this medicine. If the rash is mild (resembling scarlet fever or measles rash) and completely disappears after stopping the medicine, resume regular therapy. If the skin rash reappears upon resuming treatment, do not take this medicine again.

Potentially life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported with the use of Gamibetal Complex. These initially appear as round red spots or circular patches, often accompanied by blisters on the central trunk. Additional signs to watch for include mouth, throat, nose, or genital ulcers and conjunctivitis (red, swollen eyes).
These potentially life-threatening skin reactions are often accompanied by flu-like symptoms. The rash may progress with the development of widespread blisters or skin exfoliation. The highest risk of severe skin reactions occurs within the first weeks of treatment.
If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis while using Gamibetal Complex, Gamibetal Complex must not be used again.
If you develop a skin rash or these skin symptoms, seek urgent medical advice and inform the doctor that you are taking this medicine.
The risk of developing Stevens-Johnson syndrome during treatment with Gamibetal Complex may be associated with a genetic variant in individuals of Chinese or Thai origin.
If you belong to one of these ethnic groups and have previously been informed that you carry this genetic variant (HLA-B*1502), consult your doctor before taking Gamibetal Complex.
If you are of Taiwanese, Japanese, Malaysian, or Thai origin and tests have shown that you carry the CYP2C9*3 genetic variant.

If Gamibetal Complex is used during pregnancy, there is a risk of harm to the unborn child. Women of childbearing potential must use effective contraception during treatment with Gamibetal Complex (see "Pregnancy and breastfeeding").

Children
In early infancy, this medicine should not be used unless strictly necessary and under medical supervision.

Other medicines and Gamibetal Complex
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
When starting treatment with other antiepileptic drugs, the initial dose of this medicine should be gradually increased, and your doctor will simultaneously advise you on how to gradually reduce the dose of previously used medications.
Some medicines may alter the effect of Gamibetal Complex or may have their effects altered by this medicine, particularly:

• Certain oral anticoagulants, e.g., rivaroxaban, dabigatran, apixaban, edoxaban;
• Medicines used for alcoholism (e.g., disulfiram), anti-inflammatory drugs (e.g., phenylbutazone), antibacterial agents (e.g., sulfaphenazole and isoniazid), and barbiturates, which may interact with the phenytoin contained in this medicine;
• Taking antidepressants (tricyclic antidepressants) at high doses may increase the risk of epileptic seizures;
• Concomitant use of medicines containing Hypericum perforatum (St. John's wort) may reduce the effectiveness of this medicine;
• Valproic acid (used for seizures). Consult your doctor if you experience nausea, vomiting, agitation, confusion, seizures, drowsiness, or muscle coordination problems (symptoms of hyperammonemia);
• Lacosamide;
• Ticagrelor.

Gamibetal Complex, food, drinks, and alcohol
This medicine may enhance the effects of alcohol. As a precautionary safety measure, do not take this medicine with alcohol.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Due to the presence of phenytoin
Gamibetal Complex may cause serious birth defects. If you take Gamibetal Complex during pregnancy, the risk of your baby having a birth defect is up to 3 times higher than in women who do not take antiepileptic medicines. Serious birth defects observed include abnormalities in growth, skull, face, nails, fingers, and heart. Some of these may occur together as part of the fetal hydantoin syndrome.
Neurological development problems (brain development) have been observed in children born to mothers who took phenytoin during pregnancy. Some studies have shown that phenytoin negatively affects neurological development in children exposed to it in utero, while other studies have not found such an effect. The possibility of an effect on neurological development cannot be ruled out.
If you are a woman of childbearing potential and not planning a pregnancy, you must use an effective contraceptive method during treatment with Gamibetal Complex. Gamibetal Complex may affect how hormonal contraceptives work, such as the contraceptive pill (birth control), making them less effective in preventing pregnancy. Consult your doctor, who will advise you on the most suitable type of contraception to use during treatment with Gamibetal Complex.
If you are a woman of childbearing potential and planning a pregnancy, consult your doctor before stopping contraception and before attempting pregnancy to evaluate switching to alternative appropriate treatments to avoid fetal exposure to phenytoin.
If you are pregnant or think you might be, inform your doctor immediately. Do not stop taking the medicine until you have discussed it with your doctor. Stopping treatment without medical advice may cause seizures, which could be dangerous for both you and the fetus. Your doctor may decide to change your treatment.

Due to the presence of phenobarbital
If taken during pregnancy, phenobarbital may cause serious birth defects and may affect how the child develops during growth. Birth defects reported in studies include cleft lip (a split in the upper lip) and cleft palate (a split in the roof of the mouth), and heart abnormalities. Other birth defects reported include penile malformation (hypospadias), smaller than normal head size, and facial, nail, and finger abnormalities.
If you take phenobarbital during pregnancy, your risk of having a child with birth defects requiring medical treatment is higher than in other women. In the general population, the baseline risk of major malformations is 2–3%. This risk is approximately 3 times higher in women taking phenobarbital.
Children born to mothers who used phenobarbital during pregnancy may also be at increased risk of being smaller than expected.
Neurological developmental disorders (delays in development due to brain development disorders) have been reported in children exposed to phenobarbital during pregnancy. Studies on the risk of neurological developmental disorders remain contradictory.
Phenobarbital should not be used during pregnancy unless no equally effective alternative therapy is available.
Inform your doctor immediately if you become pregnant. Your doctor must discuss the potential effects of phenobarbital on the unborn child and carefully weigh the risks and benefits of treatment.
Do not stop taking phenobarbital until you have discussed it with your doctor, as abruptly stopping the medicine may increase the risk of seizures, which could have harmful effects on you and the unborn child.
If you have taken phenobarbital during the last trimester of pregnancy, appropriate monitoring should be conducted to detect potential problems in the newborn, such as seizures, excessive crying, muscle weakness, and sucking difficulties.

Women of childbearing potential / Contraception
If you are a woman of childbearing potential, you must use an effective contraceptive method during treatment with phenobarbital and for two months after stopping treatment. Phenobarbital may affect the functioning of hormonal contraceptives, such as the contraceptive pill, making them less effective in preventing pregnancy. Talk to your doctor, who will discuss with you the most suitable type of contraception to use while taking phenobarbital.
If you are a woman of childbearing potential and planning a pregnancy, consult your doctor before stopping contraception and before attempting pregnancy regarding switching to alternative appropriate treatments to avoid fetal exposure to phenobarbital.

Driving and using machines
This medicine may cause drowsiness and difficulty walking. Do not drive vehicles or operate machinery until you know how this medicine affects you.

3. How to use Gamibetal Complex

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose in adults is: 2 – 4 tablets per day, according to medical prescription.

Use in children and adolescents
The recommended dose is:

• up to 5 years of age: from half a tablet to 1 tablet per day, according to medical prescription;
• from 5 to 10 years of age: from 1 to 2 tablets per day, according to medical prescription;
• from 10 years of age onwards: from 2 to 4 tablets per day, according to medical prescription.
  In early infancy, this medicine should not be used unless strictly necessary and under medical supervision. The tablet may be divided into equal parts.

Elderly
If you are elderly, your doctor will prescribe the most appropriate dose for you.

If you take more Gamibetal Complex than you should
If you take too much of this medicine, contact your doctor immediately or go to the nearest hospital.
If you have taken more medicine than prescribed, you may experience: difficulty or inability to breathe (respiratory depression), impaired movement (depression of superficial and deep reflexes), constricted pupils (miosis), reduced urine production (reduced diuresis), lowered body temperature (hypothermia), and loss of consciousness up to coma.

If you stop treatment with Gamibetal Complex
Do not stop treatment with this medicine without first talking to your doctor, as this may cause sudden onset of epileptic seizures.

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

4. Possible side effects

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

The following side effects can be very serious. If you experience any of these symptoms, seek urgent medical advice and inform the doctor that you are taking this medicine, or go immediately to hospital:

• Appearance of round red spots or circular patches, often accompanied by blisters on the central part of the trunk;
• Ulcers in the mouth, throat, nose, or genitals, and conjunctivitis (red, swollen eyes), accompanied by flu-like symptoms.

These could be signs of potentially life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis), which have been reported very rarely with the use of this medicine (see section 2, "Warnings and precautions").

Rarely reported side effects are:

• Skin problems such as rashes (erythema multiforme), measles-like or scarlet fever-like rashes, and, even more rarely, rashes with blister formation, skin peeling, or redness;
• Liver problems (hepatitis and toxic hepatitis);
• Blood disorders (leucopenia, agranulocytosis, thrombocytopenia, and purpura);
• Problems with red blood cells and anaemias (macrocytosis or megaloblastic anaemia);
• Excitement, agitation, and delirium;
• Dizziness, rapid and involuntary eye movements (nystagmus), movement coordination problems (ataxia), speech disorders, confusion, muscle contractions, and headache (cephalgia). These effects resolve spontaneously when the dose is reduced;
• Mild drowsiness, dizziness, and skin rashes, which may occur at low doses of this medicine. Drowsiness and difficulty walking (gait disturbances) may occur at high doses of this medicine. These effects are due to the phenobarbital contained in the medicine;
• Nausea, vomiting, heartburn, constipation. You can avoid these effects by taking this medicine with food;
• Redness and swelling of the gums (gingival hyperplasia). This phenomenon is due to the phenytoin contained in this medicine. You can prevent or minimize it through careful and frequent oral and dental hygiene, combined with gentle gum massage and a balanced diet providing sufficient calories and vitamins;
• Bone problems (osteopenia), thinning of the bones (osteoporosis), and fractures. If you have been taking an antiepileptic medicine for a long time, if you have or have had osteoporosis, or if you are taking steroids (medicines used for inflammation or allergies), inform your doctor or pharmacist.

Side effects with unknown frequency:

• A reduction in the number of a specific type of red blood cells (red cell aplasia).

Additional side effects in children
Hyperactivity may occur in children and adolescents.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to 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.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gamibetal Complex

This medicine does not require any special storage conditions.
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 "Expiry". The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Gamibetal Complex contains

• The active substances are buxamina, phenobarbital and sodium phenytoin. Each tablet contains 250 mg of buxamina, 50 mg of phenobarbital, and 50 mg of sodium phenytoin.
• The other components are maize starch, gelatin, hydrated colloidal silica, magnesium stearate and talc.

Description of the appearance of Gamibetal Complex and contents of the pack
Gamibetal Complex is supplied in a box containing 30 tablets in blisters.
Marketing Authorization Holder and Manufacturer
Laboratorio Farmaceutico S.I.T. S.r.l. - Via Cavour, 70 - 27035 Mede (PV)