Luminale

Package leaflet: Information for the patient

LUMINALE 200 mg/ml injectable solution for intramuscular use

Phenobarbital
Please read all of 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 other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What LUMINALE is and what it is used for

LUMINALE contains the active substance phenobarbital, a sedative belonging to the group of
antiepileptic, hypnotic barbiturates.
LUMINALE is mainly indicated as a general sedative, particularly in epilepsy and in all conditions requiring prolonged sedation.
LUMINALE is especially useful in focal epilepsy and grand mal seizures.
It may also be used as a hypnotic and in detoxification from chronic barbiturate dependence (detoxification from chronic use of barbiturates, which are hypnotic-sedative substances).

2. What you should know before using LUMINALE

Do not use LUMINALE

• if you are allergic to phenobarbital, barbiturates, or any of the other ingredients of this medicine (listed in section 6).
• if you have porphyria
• if you suffer from renal or hepatic insufficiency
• if you have heart problems (severe cardiopathy)
• if you are experiencing acute intoxication from alcohol, analgesics, or hypnotics.
• if you are taking daclatasvir, dasabuvir, paritaprevir, ombitasvir, ledipasvir, sofosbuvir (medicines used against HIV virus and hepatitis C virus) (see "Other medicines and LUMINALE").

Warnings and precautions
Talk to your doctor or pharmacist before using LUMINALE.
A small number of patients treated with antiepileptic medicines such as LUMINALE have developed self-harming thoughts or suicidal ideation. If such thoughts occur at any time, contact your doctor immediately.
Phenobarbital may lead to dependence. Prolonged therapy induces the formation of liver enzymes that accelerate the metabolism of certain drugs, for example anticoagulants, some antibiotics, adrenal steroids (hormones produced by the adrenal glands located above the kidneys), etc.
Preparations based on Hypericum perforatum (also known as St. John's wort) should not be taken concurrently with medicines containing phenobarbital due to the risk of decreased plasma levels and reduced therapeutic efficacy of phenobarbital (see section “Other medicines and LUMINALE”).
Abrupt discontinuation of treatment in epileptic patients may trigger status epilepticus.
Potentially life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome) have been reported with the use of LUMINALE. These initially appear as round red spots or circular patches, often accompanied by blisters on the central trunk.
Additional symptoms to watch for include mouth ulcers, sore throat, nasal ulcers, genital ulcers, and conjunctivitis (red and swollen eyes).
These potentially life-threatening skin reactions are often accompanied by flu-like symptoms. The rash may progress to widespread blistering or skin exfoliation.
DRESS syndrome is also associated with changes in blood test values (haematological parameters), swollen lymph nodes, and internal organ involvement, such as liver dysfunction.
The highest risk of developing severe skin reactions occurs within the first 8 weeks of treatment.
If you have previously experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome while taking phenobarbital-containing medicines, LUMINALE must not be used again.
If you develop a skin rash or any of these skin symptoms, stop taking LUMINALE immediately, seek urgent medical advice, and inform the doctor that you are taking this medicine.

Other medicines and LUMINALE
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicines.
The effects of LUMINALE may be influenced by, or may influence, the following medicines.
The combination of LUMINALE with the following medicines is contraindicated:

• Daclatasivir, dasabuvir, paritaprevir, ombitasvir, ledipasvir, sofosbuvir (used against HIV virus and hepatitis C virus), due to the potential reduction in their efficacy.

The combination of LUMINALE with the following medicines is not recommended:
St. John's wort (Hypericum perforatum): the efficacy of phenobarbital may be reduced by concomitant administration of Hypericum perforatum preparations. This is due to the induction of drug-metabolizing enzymes by Hypericum perforatum, which therefore should not be administered concurrently with phenobarbital. The enzyme-inducing effect may persist for at least 2 weeks after discontinuation of Hypericum perforatum treatment. If a patient is taking Hypericum perforatum products concurrently, blood levels of phenobarbital should be monitored and Hypericum perforatum therapy should be discontinued. Blood levels of phenobarbital may increase after stopping Hypericum perforatum. The phenobarbital dosage may require adjustment.
Oestrogen-progestogen and progestogen-only contraceptives (hormonal contraceptives), because LUMINALE reduces contraceptive effectiveness. If you are taking LUMINALE, you should use an alternative contraceptive method, such as a barrier method (mechanical contraception). (See section “Pregnancy and breastfeeding”).

LUMINALE and alcohol
The effect of alcohol is enhanced; therefore, consumption of alcoholic beverages should be limited.
Combination of LUMINALE with the following medicines requires special caution (in some cases, your doctor may adjust doses):

• Cyclosporine (used to prevent organ transplant rejection), because LUMINALE reduces its effect.
• Corticosteroids (glucocorticoids, mineralocorticoids, used for inflammation, certain diseases such as Addison’s disease, and in transplant patients), because LUMINALE reduces their effect.
• Levothyroxine (used for thyroid disorders), because your doctor may need to adjust the dosage.
• Theophylline and all theophylline derivatives (used for asthma), because LUMINALE reduces their effect.
• Folic acid (used for anaemias), because it reduces the effect of LUMINALE.
• Valproic acid (used for seizures), because it increases the effect of LUMINALE. Conversely, LUMINALE decreases the effect of valproic acid. Contact your doctor if you experience excessive drowsiness (sedation). Your doctor may perform blood tests to measure LUMINALE and valproic acid levels. Contact your doctor if you experience nausea, vomiting, agitation, confusion, seizures, drowsiness, or impaired muscle coordination (symptoms of hyperammonaemia).
• Warfarin/dicoumarol (oral anticoagulants used to thin the blood), because LUMINALE reduces their effect.
• Imipramine-type antidepressants (used for depression), because they may promote the occurrence of seizures (generalized convulsive seizures).
• Chloramphenicol, dextropropoxyphene: these drugs may increase plasma levels of phenobarbital, potentially increasing phenobarbital toxicity.
• Antacids: these drugs may reduce intestinal absorption of phenobarbital, resulting in reduced antiepileptic efficacy and possible worsening of seizures.
• Phenytoin (used for seizures), because LUMINALE may alter its blood levels.
• Carbamazepine (used for seizures), because LUMINALE reduces its blood levels.
• Benzodiazepines: phenobarbital may increase the metabolism and reduce plasma concentrations of benzodiazepines; dosage adjustment may be necessary.
• Haloperidol and other neuroleptics: phenobarbital may increase the metabolism and reduce plasma concentrations of haloperidol and other neuroleptics; dosage adjustment may be necessary.
• Griseofulvin: phenobarbital may increase the metabolism and reduce plasma concentrations of griseofulvin, resulting in reduced antifungal activity.
• Paroxetine, reboxetine: phenobarbital may reduce plasma levels of these drugs.

Other combinations to consider

• Anticancer drugs: phenobarbital may increase the metabolism of anticancer drugs and reduce their therapeutic efficacy.

Pregnancy, breastfeeding, and fertility
Pregnancy
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
The need for antiepileptic treatment should be reassessed when a woman plans a pregnancy. Women of childbearing age should be informed about the risks and benefits associated with the use of phenobarbital during pregnancy.
The risk of congenital malformations is increased (by 2 to 3 times) in children born to mothers treated with antiepileptic drugs; the most frequently reported malformations include cleft lip, cardiovascular malformations, and neural tube defects (a part of the embryo that develops into the brain and spinal cord).
Polytherapy (treatment with multiple drugs) with antiepileptic medicines may be associated with a higher risk of congenital malformations compared to monotherapy. Therefore, monotherapy should be used whenever possible.
Abrupt discontinuation of antiepileptic therapy should be avoided due to the risk of seizure recurrence, which could have serious consequences for both mother and child.
Women of childbearing age must use an effective contraceptive method continuously throughout LUMINALE treatment and for two months after stopping treatment. Phenobarbital may interact with oestrogen-progestogen and progestogen-only contraceptives (used as contraceptives), reducing contraceptive efficacy due to increased hepatic catabolism. Therefore, an alternative contraceptive method, preferably a mechanical one, should be used.
If a woman is planning a pregnancy, she should consider switching to an appropriate alternative treatment before conception. If a woman becomes pregnant, the risks and benefits of LUMINALE treatment for both mother and fetus should be carefully evaluated to determine whether treatment can continue or should be replaced with an appropriate alternative. If LUMINALE treatment continues, use the lowest effective dose.
In utero exposure to phenobarbital may potentially cause cognitive and neurological impairments in the child.
Folic acid supplementation during pregnancy may help reduce the risk of neurological defects in the newborn.

Breastfeeding
Phenobarbital crosses the placental barrier and is excreted in breast milk. Therefore, there is a small risk of sedation in the newborn. Breastfeeding is therefore not recommended.

Fertility
Phenobarbital increases plasma concentration of sex hormone-binding globulin (SHBG) in both sexes. This may lead to reduced biologically active plasma levels of testosterone and estradiol, resulting in menstrual disorders, sexual dysfunction, and reduced fertility.

Driving and using machines
This medicine impairs the ability to drive or operate machinery, as it reduces attention and prolongs reaction time. Therefore, avoid driving or operating machinery during treatment.

LUMINALE 200 mg/ml solution for injection for intramuscular use contains 700 mg of propylene glycol per vial. If the child is less than 4 weeks old, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol. LUMINALE 200 mg/ml solution for injection for intramuscular use also contains small amounts of ethanol (alcohol), less than 100 mg per vial.

3. How to use LUMINALE

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Unless otherwise prescribed by the doctor, the recommended dose in adults is one vial per day administered
intramuscularly. Do not exceed 400 mg in 24 hours. In children, 10 mg per year of age starting from
1 year of age.
In the treatment of elderly patients, the dosage must be carefully determined by the doctor, who will evaluate whether a reduction of the above-mentioned doses is necessary.
If you use more LUMINALE than you should
Treatment of acute barbiturate intoxication involves immediate gastric lavage, if the patient's condition allows it.
Removal of already absorbed drug can be achieved through forced diuresis (use of diuretics to increase urine production) and urine alkalization (reduction of acidity). In more severe cases, hemodialysis (artificial blood purification) may be useful, and mechanical control of respiration may be necessary. Administration of antibiotics is required to prevent the onset of pulmonary complications.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
For congenital malformations, see section "Pregnancy".

Rare side effects (may affect more than 1 in 1,000 people)

• allergic dermatitis, erythema multiforme, severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
• toxic hepatitis
• leucopenia (reduction in white blood cells), agranulocytosis (severe reduction in white blood cells), thrombocytopenia (reduction in platelets, which are small cell components necessary for blood clotting), and purpura (small spots of bleeding under the skin)
• excitement, agitation, and delirium. In paediatric patients, manifestations of psychomotor hyperactivity (inattention and impulsiveness) may occur

Very rare side effects (may affect up to 1 in 10,000 people)

• drug reaction with eosinophilia and systemic symptoms (DRESS)

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• aplastic anaemia
• vitamin K-responsive hypoprothrombinaemia (reduction in prothrombin, necessary for blood clotting) may occur in newborns of mothers treated with phenobarbital
• During long-term treatment, megaloblastic anaemia (reduction and increased size of red blood cells) responsive to folate treatment, and osteomalacia (loss of calcium from bones) responsive to vitamin D treatment may occur
• Sedation, ataxia (disorder of coordination of voluntary movements, which are performed without precision and with errors in direction), nystagmus (rapid, involuntary eye movements), and confusion may occur, especially in elderly patients, following administration of high doses
• Cases of bone disease including osteopenia and osteoporosis (thinning of bones due to loss of calcium and phosphates) and fractures (resulting from calcium loss) have been reported. Contact your doctor or pharmacist if you are on long-term treatment with an antiepileptic medicine, or if you have a history of osteoporosis, or if you are taking steroids
• Mood changes, attention disturbance, confusional state

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via
reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store LUMINALE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after Exp.
The expiry date refers to the product in its original, unopened packaging, correctly stored.
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 you no longer use. This will help protect the environment.

6. Package contents and other information

What LUMINALE contains

• The active substance is phenobarbital. Each vial contains 200 mg of phenobarbital (equivalent to 219 mg of sodium phenobarbital).
• The other components are: propylene glycol, ethanol, water for injections.

Description of the appearance of LUMINALE and contents of the pack
Box of 10 vials

Marketing Authorization Holder
SUBSTIPHARM 24 rue Erlanger, 75016 Paris - France

Sales Licensee
SUBSTIPHARM S.r.l. Via Felice Casati, 20 – 20124 Milan, Italy

Manufacturer
Famar Italia S.p.A. – Via Zambeletti, 25 – 20021 Baranzate (MI)

Package leaflet: information for the patient

LUMINALE 100 mg tablets

Phenobarbital
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 other people, 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, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What LUMINALE is and what it is used for

LUMINALE contains the active substance phenobarbital, a sedative belonging to the group of antiepileptic, barbiturate hypnotic drugs.
LUMINALE is primarily indicated as a general sedative, particularly in epilepsy and in all conditions requiring prolonged sedation.
LUMINALE is especially useful in focal epilepsy and grand mal.
It may also be used as a hypnotic and in the detoxification of chronic barbiturism (detoxification from chronic use of barbiturates, hypnotic-sedative substances).

2. What you should know before taking LUMINALE

Do not take LUMINALE

• if you are allergic to phenobarbital, barbiturates, or any of the other ingredients of this medicine (listed in section 6);
• if you have porphyria;
• if you suffer from renal or hepatic insufficiency;
• if you have heart problems (severe cardiopathy);
• if you have acute intoxication from alcohol, analgesics, or hypnotics;
• if you are taking daclatasvir, dasabuvir, paritaprevir, ombitasvir, ledipasvir, sofosbuvir (medicines used against HIV virus and hepatitis C virus) (see "Other medicines and LUMINALE").

Warnings and precautions
Talk to your doctor or pharmacist before taking LUMINALE.
A small number of patients treated with antiepileptic medicines such as LUMINALE have developed self-harming thoughts or suicidal ideation. If such thoughts occur at any time, contact your doctor immediately.
Phenobarbital may lead to dependence. Prolonged therapy induces the formation of liver enzymes that accelerate the metabolism of certain drugs, for example anticoagulants, some antibiotics, adrenal steroids (hormones produced by the adrenal glands located above the kidneys), etc.
Preparations containing Hypericum perforatum (also known as St. John's wort) should not be taken concurrently with medicines containing phenobarbital due to the risk of decreased plasma levels and reduced therapeutic efficacy of phenobarbital (see section “Other medicines and LUMINALE”).
Abrupt discontinuation of treatment in epileptic patients may trigger status epilepticus.
Potentially life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome) have been reported with the use of LUMINALE. These initially appear as round red spots or circular patches, often accompanied by blisters on the central trunk.
Additional symptoms to watch for include mouth, throat, nose, or genital ulcers, and conjunctivitis (red and 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.
DRESS syndrome is also associated with changes in blood test values (blood count), enlarged lymph nodes, and abnormalities in other internal organs, such as the liver.
The highest risk of developing severe skin reactions occurs within the first 8 weeks of treatment.
If you have previously experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome while taking phenobarbital-containing medicines, LUMINALE must not be reused.
If you develop a skin rash or these skin symptoms, stop taking LUMINALE immediately, urgently consult a doctor, and inform them that you are taking this medicine.
Phenobarbital may be associated with cognitive disturbances and negative effects on mood (e.g., depressive symptoms), impacting well-being and quality of life. Patients should be monitored for these potential effects.
Antiepileptic drugs, including phenobarbital, as well as epilepsy itself, may cause disturbances in sex hormones. Hormonal effects induced by epilepsy or antiepileptic drugs should be considered when initiating antiepileptic therapy, especially if long-term treatment is anticipated.

Other medicines and LUMINALE
Inform your doctor or pharmacist if you are currently taking, have recently taken, or might take any other medicines.
The effects of LUMINALE may be influenced by, or may influence, the following medicines.
The combination of LUMINALE with the following medicines is contraindicated:

• Daclatasivir, dasabuvir, paritaprevir, ombitasvir, ledipasvir, sofosbuvir (used against HIV virus and hepatitis C virus), due to the possible reduction in their efficacy.

The combination of LUMINALE with the following medicines is not recommended:
St. John's wort (Hypericum perforatum): the efficacy of phenobarbital may be reduced by concomitant administration of Hypericum perforatum preparations. This is due to the induction of drug-metabolizing enzymes by Hypericum perforatum preparations, which therefore should not be administered concurrently with phenobarbital. The enzyme-inducing effect may persist for at least 2 weeks after discontinuation of Hypericum perforatum treatment. If a patient is concurrently taking Hypericum perforatum products, blood levels of phenobarbital should be monitored and Hypericum perforatum treatment should be discontinued. Blood levels of phenobarbital may increase upon discontinuation of Hypericum perforatum. Dose adjustment of phenobarbital may be necessary.
Estrogen-progestins and progestins (hormones used as contraceptives), because LUMINALE reduces contraceptive effectiveness. If you are taking LUMINALE, you should use a different contraceptive method, such as a barrier method (mechanical contraception) (see section “Pregnancy and breastfeeding”).

LUMINALE and alcohol
The effect of alcohol is enhanced; therefore, consumption of alcoholic beverages should be limited.
The combination of LUMINALE with the following medicines requires special caution (in some cases, your doctor may adjust the doses):

• Cyclosporine (used to prevent organ transplant rejection), because LUMINALE reduces its effect.
• Corticosteroids (glucocorticoids, mineralocorticoids, used for inflammation, certain diseases such as Addison's disease, and in transplant patients), because LUMINALE reduces their effect.
• Levothyroxine (used for thyroid disorders), because your doctor may need to adjust the dosage.
• Theophylline and all theophylline derivatives (used for asthma), because LUMINALE reduces their effect.
• Folic acid (used for anemias), because it reduces the effect of LUMINALE.
• Valproic acid (used for seizures), because it increases the effect of LUMINALE. Conversely, LUMINALE reduces the effect of valproic acid. Contact your doctor if you experience excessive drowsiness (sedation). Your doctor may perform blood tests to measure LUMINALE and valproic acid levels. Contact your doctor if you experience nausea, vomiting, agitation, confusion, seizures, somnolence, or muscle coordination problems (symptoms of hyperammonemia).
• Warfarin/dicoumarol (oral anticoagulants, used to thin the blood), because LUMINALE reduces their effect.
• Imipramine-type antidepressants (used for depression), because they may promote the occurrence of seizures (generalized convulsive seizures).
• Chloramphenicol, dextropropoxyphene: these drugs may increase phenobarbital plasma levels, potentially increasing phenobarbital toxicity.
• Antacids: these drugs may reduce intestinal absorption of phenobarbital, leading to reduced antiepileptic efficacy and possible worsening of seizures.
• Phenytoin (used for seizures), because LUMINALE may alter its blood levels.
• Carbamazepine (used for seizures), because LUMINALE reduces its blood concentration.
• Benzodiazepines: phenobarbital may increase the metabolism and reduce plasma concentrations of benzodiazepines; dose adjustment of these drugs may be necessary.
• Haloperidol and other neuroleptics: phenobarbital may increase the metabolism and reduce plasma concentrations of haloperidol and other neuroleptics; dose adjustment may be necessary.
• Griseofulvin: phenobarbital may increase the metabolism and reduce plasma concentrations of griseofulvin, resulting in reduced antifungal activity.
• Paroxetine, reboxetine: phenobarbital may reduce plasma levels of these drugs.

Other combinations to consider:

• Anticancer drugs: phenobarbital may increase the metabolism of anticancer drugs and reduce their therapeutic efficacy.

Pregnancy, breastfeeding, and fertility
Pregnancy
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
The need for antiepileptic treatment should be reassessed when pregnancy is planned. Women of childbearing potential should be informed of the risks and benefits associated with the use of phenobarbital during pregnancy.
The risk of congenital malformations is increased (by 2 to 3 times) in children born to mothers treated with antiepileptic drugs; the most commonly reported defects include cleft lip, cardiovascular malformations, and neural tube defects (the embryonic structure that develops into the brain and spinal cord).
Polytherapy (treatment with multiple drugs) with antiepileptic medicines may be associated with a higher risk of congenital malformations compared to monotherapy. Therefore, monotherapy should be used whenever possible.
Abrupt discontinuation of antiepileptic therapy should be avoided due to the risk of seizure recurrence, which could have serious consequences for both mother and child.
Women of childbearing potential must use an effective contraceptive method consistently throughout LUMINALE treatment and for two months after its discontinuation. Phenobarbital may interact with estrogen-progestins and progestins (used as contraceptives), reducing contraceptive efficacy due to increased hepatic catabolism. Therefore, a different contraceptive method, preferably mechanical, should be used.
If a woman plans a pregnancy, she should consider switching to an appropriate alternative treatment before conception. If a woman becomes pregnant, the risks and benefits of LUMINALE treatment for both mother and fetus should be carefully evaluated to determine whether treatment should continue or be replaced with an appropriate alternative. If LUMINALE treatment must continue, use the lowest effective dose.
In utero exposure to phenobarbital may potentially cause cognitive and neurological alterations in the child.
Folic acid supplementation during pregnancy may help reduce the risk of neurological defects in the newborn.

Breastfeeding
Phenobarbital crosses the placental barrier and is therefore excreted in breast milk. Consequently, there is a small risk of sedation in the newborn. Breastfeeding is therefore not recommended.

Fertility
Phenobarbital increases plasma levels of sex hormone-binding globulin (SHBG) in both sexes. This may lead to reduced biologically active plasma levels of testosterone and estradiol, resulting in menstrual disorders, sexual dysfunction, and reduced fertility.

Driving and using machines
This medicine impairs the ability to drive or operate machinery, as it reduces attention and slows reaction time. Therefore, avoid driving or operating machinery during treatment.

3. How to take LUMINALE

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
As a sedative, the recommended dose is 50 to 100 mg (half to one tablet) daily. As an anticonvulsant, the recommended dose in adults is 100 to 300 mg (1-3 tablets) daily, divided into two or three doses. In children, doses should be reduced (from 100 to 20 mg) according to age and weight, and LUMINALE 15 mg tablets are recommended.
For severe insomnia, the recommended dose is 50 to 200 mg (half to two tablets) at bedtime, one hour before going to sleep. The tablets may be crushed into a small amount of water or, if necessary, added to food.
In the treatment of elderly patients, dosage must be carefully determined by the doctor, who should consider a possible reduction of the above-mentioned doses.
If you take more LUMINALE than you should
Treatment of acute barbiturate intoxication involves immediate gastric lavage, if the patient's condition allows.
Removal of already absorbed drug may be achieved by forced diuresis (use of diuretics to increase urine production) and urine alkalization (reduction of acidity). In more severe cases, hemodialysis (artificial blood purification) may be useful, and mechanical control of respiration may be necessary. Administration of antibiotics is required to prevent the onset of pulmonary complications.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
For congenital malformations, see section "Pregnancy".

Rare side effects (may affect more than 1 in 1,000 people)

• allergic dermatitis, erythema multiforme, severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
• toxic hepatitis
• leucopenia (reduction in white blood cells), agranulocytosis (severe reduction in white blood cells), thrombocytopenia (reduction in platelets, which are small cell fragments necessary for blood clotting), and purpura (small spots of bleeding under the skin)
• excitement, agitation, and delirium. In paediatric patients, manifestations of psychomotor hyperactivity (inattention and impulsiveness) may occur

Very rare side effects (may affect up to 1 in 10,000 patients)

• drug reaction with eosinophilia and systemic symptoms (DRESS)

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• aplastic anaemia
• hypoprothrombinemia (reduction in prothrombin, necessary for blood clotting), which is responsive to vitamin K therapy, may occur in newborns of mothers treated with phenobarbital
• During chronic treatment, megaloblastic anaemia (reduction and enlargement of red blood cells) responsive to folate treatment and osteomalacia (loss of calcium from bones) responsive to vitamin D treatment may occur
• Sedation, ataxia (disorder of coordination of voluntary movements, which become unmeasured and inaccurate), nystagmus (rapid, involuntary eye movements), and confusion may occur, especially in elderly patients, following administration of high doses
• Cases of bone disease including osteopenia and osteoporosis (thinning of bones due to loss of calcium and phosphates) and fractures (resulting from calcium loss) have been reported. Contact your doctor or pharmacist if you are on long-term treatment with an antiepileptic medicine, or if you have a history of osteoporosis, or if you are taking steroids
• Mood changes, attention disturbance, confusion state

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via
reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store LUMINALE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after Exp.
The expiry date refers to the product in its original, unopened packaging and properly stored.
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 you no longer use. This will help protect the environment.

6. Package contents and other information

What LUMINALE contains

• 1 tablet contains 100 mg of phenobarbital.
• The other components are: talc, povidone, stearic acid, maize starch.

Description of the appearance of LUMINALE and pack contents
Carton containing 20 tablets
Marketing Authorization Holder
SUBSTIPHARM 24 rue Erlanger, 75016 Paris - France
Selling Licensee
SUBSTIPHARM S.r.l. Via Felice Casati, 20 – 20124 Milano
Manufacturers
Famar Italia S.p.A. – Via Zambeletti, 25 – 20021 Baranzate (MI)
Patient Information Leaflet

LUMINALE 15 mg tablets

Phenobarbital
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 other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What LUMINALE is and what it is used for

LUMINALE contains the active substance phenobarbital, a sedative belonging to the group of
antiepileptic, barbiturate hypnotics.
LUMINALE is primarily indicated as a general sedative, particularly in epilepsy and all conditions requiring prolonged sedation.
LUMINALE is especially useful in focal epilepsy and grand mal. However, the low dosage of phenobarbital present in the preparation allows adequate blood levels to be achieved only in children. LUMINALE may also be used as a hypnotic.

2. What you should know before taking LUMINALE

Do not take LUMINALE

• if you are allergic to phenobarbital, barbiturates, or any of the other ingredients of this medicine (listed in section 6).
• if you have porphyria
• if you suffer from renal or hepatic insufficiency
• if you have heart problems (severe heart disease)
• if you are experiencing acute intoxication from alcohol, analgesics, or hypnotics
• if you are taking daclatasvir, dasabuvir, paritaprevir, ombitasvir, ledipasvir, sofosbuvir (medicines used against HIV virus and hepatitis C virus) (see "Other
• medicines and LUMINALE").

Warnings and precautions
Talk to your doctor or pharmacist before taking LUMINALE.
A small number of patients treated with antiepileptic medicines such as LUMINALE have developed self-harming thoughts or suicidal ideation. If such thoughts occur at any time, contact your doctor immediately.
Phenobarbital may cause dependence. Prolonged therapy induces the formation of liver enzymes that accelerate the metabolism of certain drugs, for example anticoagulants, some antibiotics, adrenal steroids (hormones produced by the adrenal glands located above the kidneys), etc.
Preparations containing Hypericum perforatum (also known as St. John's wort) should not be taken concomitantly with medicines containing phenobarbital due to the risk of decreased plasma levels and reduced therapeutic efficacy of phenobarbital (see section “Other medicines and LUMINALE”).
Abrupt discontinuation of treatment in epileptic patients may lead to status epilepticus.
Potentially life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome) have been reported with the use of LUMINALE. These initially appear as round red spots or circular patches, often accompanied by blisters, mainly on the trunk.
Additional signs to watch for include ulcers in the mouth, throat, nose, or genitals, and conjunctivitis (red and swollen eyes).
These potentially life-threatening skin reactions are often accompanied by flu-like symptoms. The rash may progress with widespread blistering or skin peeling.
DRESS syndrome is also associated with changes in blood test values (haemogram), swollen lymph nodes, and involvement of other internal organs, such as the liver.
The highest risk of developing severe skin reactions occurs during the first 8 weeks of treatment.
If you have previously experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome while using phenobarbital-containing medicines, LUMINALE must not be used again.
If you develop a skin rash or any of these skin symptoms, stop taking LUMINALE immediately, consult a doctor urgently, and inform them that you are taking this medicine.

Other medicines and LUMINALE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effects of LUMINALE may be influenced by, or may influence, the following medicines.
The combination of LUMINALE with the following medicines is contraindicated:

• Daclatasivir, dasabuvir, paritaprevir, ombitasvir, ledipasvir, sofosbuvir (used against HIV virus and hepatitis C virus), due to the possible reduction of their efficacy.

The combination of LUMINALE with the following medicines is not recommended:
St. John's wort (Hypericum perforatum): the efficacy of phenobarbital may be reduced by concomitant administration of Hypericum perforatum preparations. This is due to the induction of drug-metabolizing enzymes by Hypericum perforatum preparations, which therefore should not be administered concurrently with phenobarbital. The enzyme-inducing effect may persist for at least 2 weeks after discontinuation of Hypericum perforatum treatment. If a patient is taking Hypericum perforatum products concurrently, blood levels of phenobarbital should be monitored and Hypericum perforatum treatment should be discontinued. Blood levels of phenobarbital may increase after stopping Hypericum perforatum. The phenobarbital dose may need adjustment.
Estrogen-progestogen and progestogen-only hormonal contraceptives, because LUMINALE reduces their contraceptive effectiveness. If you are taking LUMINALE, you must use a different contraceptive method, such as a barrier method (mechanical contraception). (See section “Pregnancy and breastfeeding”).

LUMINALE and alcohol
The effect of alcohol is enhanced; consumption of alcoholic beverages should be limited.
Combination of LUMINALE with the following medicines requires special caution (in some cases, your doctor may adjust doses):

• Cyclosporine (used to prevent organ transplant rejection), because LUMINALE reduces its effect.
• Corticosteroids (gluco-mineralocorticoids, used for inflammation, certain diseases such as Addison's disease, and in transplant patients), because LUMINALE reduces their effect.
• Levothyroxine (used for thyroid disorders), because your doctor may need to adjust the dosage.
• Theophylline and all theophylline derivatives (used for asthma), because LUMINALE reduces their effect.
• Folic acid (used for anaemias), because it reduces the effect of LUMINALE.
• Valproic acid (used for seizures), because it increases the effect of LUMINALE. In turn, LUMINALE reduces the effect of valproic acid. Contact your doctor if you experience excessive drowsiness (sedation). Your doctor may perform blood tests to measure LUMINALE and valproic acid levels. Contact your doctor if you experience nausea, vomiting, agitation, confusion, seizures, drowsiness, or muscle coordination problems (symptoms of hyperammonaemia).
• Warfarin/dicoumarol (oral anticoagulants, used to thin the blood), because LUMINALE reduces their effect.
• Imipramine-type antidepressants (used for depression), because they may promote the occurrence of seizures (generalized convulsive seizures).
• Chloramphenicol, dextropropoxyphene: these drugs may increase plasma levels of phenobarbital, potentially increasing phenobarbital toxicity.
• Antacids: these drugs may reduce intestinal absorption of phenobarbital, leading to reduced antiepileptic efficacy and possible worsening of seizures.
• Phenytoin (used for seizures), because LUMINALE may alter its blood levels.
• Carbamazepine (used for seizures), because LUMINALE reduces its blood levels.
• Benzodiazepines: phenobarbital may increase the metabolism and reduce plasma concentrations of benzodiazepines; adjust dose if necessary.
• Haloperidol and other neuroleptics: phenobarbital may increase the metabolism and reduce plasma concentrations of haloperidol and other neuroleptics; adjust dose if necessary.
• Griseofulvin: phenobarbital may increase the metabolism and reduce plasma concentrations of griseofulvin, resulting in reduced antifungal activity.
• Paroxetine, reboxetine: phenobarbital may reduce plasma levels of these drugs.

Other combinations to consider

• Anticancer drugs: phenobarbital may increase the metabolism of anticancer drugs and reduce their therapeutic efficacy.

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

Pregnancy
The need for antiepileptic treatment should be reassessed when a woman plans a pregnancy. Women of childbearing age must be informed about the risks and benefits associated with the use of phenobarbital during pregnancy.
The risk of congenital malformations is increased (by 2 to 3 times) in children born to mothers treated with antiepileptic drugs; the most commonly reported malformations include cleft lip, cardiovascular malformations, and neural tube defects (the part of the embryo that develops into the brain and spinal cord).
Polytherapy (treatment with multiple drugs) with antiepileptic medicines may be associated with a higher risk of congenital malformations compared to monotherapy. Therefore, monotherapy should be practiced whenever possible.
Abrupt discontinuation of antiepileptic therapy should be avoided due to the risk of seizure recurrence, which could have serious consequences for both mother and child.
Women of childbearing age must use an effective contraceptive method consistently throughout LUMINALE treatment and for two months after stopping treatment. Phenobarbital may interact with estrogen-progestogen and progestogen-only contraceptives, reducing contraceptive efficacy due to increased hepatic catabolism. Therefore, a different contraceptive method, preferably a mechanical one, should be used.
If a woman plans a pregnancy, she should consider switching to an appropriate alternative treatment before conception. If a woman becomes pregnant, the risks and benefits of LUMINALE treatment for both mother and fetus must be carefully evaluated to determine whether treatment can continue or should be replaced with an appropriate alternative. If LUMINALE treatment must continue, use the lowest effective dose.
In utero exposure to phenobarbital may potentially cause cognitive and neurological impairments in the child.
Folic acid supplementation during pregnancy may help reduce the risk of neurological defects in the newborn.

Breastfeeding
Phenobarbital crosses the placental barrier and is excreted in breast milk. Consequently, there is a small risk of sedation in the newborn. Therefore, breastfeeding is not recommended.

Fertility
Phenobarbital increases plasma levels of sex hormone-binding globulin (SHBG) in both sexes. This may lead to reduced biologically active plasma levels of testosterone and estradiol, resulting in menstrual disorders, sexual problems, and reduced fertility.

Driving and using machines
This medicine impairs the ability to drive or operate machinery because it reduces attention and slows reaction time. Therefore, avoid driving or operating machinery during treatment.

3. How to take LUMINALE

Take this medicine exactly as prescribed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Unless otherwise prescribed by the doctor, the recommended dose is 1 to 3 tablets three times a day.
In the treatment of elderly patients, the dosage must be carefully determined by the doctor, who will evaluate whether a reduction of the above-mentioned doses should be considered.
If you take more LUMINALE than you should
Treatment of acute barbiturate intoxication involves immediate gastric lavage, if the patient's condition allows it.
Removal of already absorbed drug can be achieved through forced diuresis (use of diuretics to increase urine production) and urine alkalization (reduction of acidity). In more severe cases, hemodialysis (artificial blood purification) may be useful, and mechanical control of respiration may be necessary. Administration of antibiotics is required to prevent the onset of pulmonary complications.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
For congenital malformations, see section "Pregnancy".

Rare side effects (may affect more than 1 in 1,000 people)

• allergic dermatitis, erythema multiforme, severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
• toxic hepatitis
• leucopenia (reduction in white blood cells), agranulocytosis (severe reduction in white blood cells), thrombocytopenia (reduction in platelets, which are small cell components necessary for blood clotting), and purpura (small spots of bleeding under the skin)
• excitement, agitation, and delirium. In paediatric patients, psychomotor hyperactivity (inattention and impulsiveness) may occur

Very rare side effects (may affect up to 1 in 10,000 people)

• drug reaction with eosinophilia and systemic symptoms (DRESS)

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• aplastic anaemia
• vitamin K-responsive hypoprothrombinemia (reduction in prothrombin, necessary for blood clotting) may occur in newborns of mothers treated with phenobarbital. During chronic treatment, megaloblastic anaemia (reduction and increased size of red blood cells) responsive to folate therapy and osteomalacia (loss of calcium from bones) responsive to vitamin D treatment may occur.
• Sedation, ataxia (disorder of coordination of voluntary movements, which become unmeasured and inaccurate), nystagmus (rapid, involuntary eye movements), and mental confusion may occur, especially in elderly patients, following administration of high doses.
• Cases of bone disease including osteopenia and osteoporosis (thinning of bones due to loss of calcium and phosphates) and fractures (as a consequence of calcium loss) have been reported. Contact your doctor or pharmacist if you are on long-term treatment with an antiepileptic medicine, or if you have a history of osteoporosis, or if you are taking steroids.
• Mood alterations, attention disturbances, confusional state

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system: reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store LUMINALE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp.".
The expiry date refers to the product in its original packaging, correctly stored.
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 you no longer use. This will help protect the environment.

6. Package contents and other information

What LUMINALE contains

• The active substance is phenobarbital. Each tablet contains 15 mg of phenobarbital.
  The other ingredients are: talc, povidone, stearic acid, maize starch.

Description of the appearance of LUMINALE and contents of the pack
Carton pack containing 30 tablets.

Marketing Authorization Holder
SUBSTIPHARM 24 rue Erlanger, 75016 Paris - France

Sales Licensee
SUBSTIPHARM S.r.l. Via Felice Casati, 20 – 20124 Milan

Manufacturer
Famar Italia S.p.A. – Via Zambeletti, 25 – 20021 – Baranzate (MI)