GARDENALE

Patient Information Leaflet

Gardenale 50 mg tablets, 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, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Gardenale is and what it is used for

Gardenale contains phenobarbital, which belongs to a class of medicines called
"antiepileptic barbiturates".
Gardenale is indicated in epilepsy, for the treatment of violent and involuntary muscle contractions known as convulsions (particularly tonic-clonic seizures of grand mal and focal cortical seizures).
Gardenale may be used to detoxify from prolonged use of barbiturates (chronic barbiturism).

2. What you should know before taking Gardenale

Do not take Gardenale

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

Warnings and precautions

It is important to read this section carefully if you are to take this medicine.

Talk to your doctor or pharmacist before taking Gardenale.

Serious skin reactions have been reported with Gardenale, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP):

• Symptoms of SJS or TEN may include blisters, peeling or bleeding of the skin on any part of the body (including lips, eyes, mouth, nose, genitals, hands or feet), with or without rash. You may also experience flu-like symptoms such as fever, chills, or muscle pain.
• Symptoms and signs of DRESS may include flu-like symptoms and widespread rash accompanied by high body temperature and swollen lymph nodes. Abnormal blood test results may include increased liver enzyme levels, increased levels of a type of white blood cells (eosinophilia), and swollen lymph nodes.
• Symptoms of AGEP appear early in treatment and may include widespread red, scaly skin rash with bumps under the skin (including skin folds, chest, abdomen (including stomach area), back, and arms), blisters, and fever. The highest risk of developing severe skin reactions occurs during the first weeks of treatment. If you develop severe skin reactions or any of the reactions listed above, contact your doctor or healthcare provider immediately. If you have previously developed Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS while using phenobarbital-containing medicines, you must not use this medicine again.

Gardenale may lead to dependence (reduced effectiveness).

Prolonged therapy may interfere with certain medicines, for example, medicines used to thin the blood (anticoagulants), some antibiotics, some anti-inflammatory medicines (adrenal corticosteroids), etc.

Your doctor will prescribe Gardenale cautiously if you are also taking other medicines such as those used to treat psychiatric disorders (psychotropic drugs) or medicines used for allergies (antihistamines).

Do not take St. John’s wort (Hypericum perforatum) preparations at the same time as medicines containing phenobarbital, such as Gardenale, as St. John’s wort may reduce their activity (see "Other medicines and Gardenale").

Do not abruptly stop treatment with Gardenale, as epileptic seizures may occur in patients with epilepsy.

Your doctor will prescribe a reduced dose of Gardenale if you have kidney problems (renal insufficiency), liver problems (hepatic insufficiency), if you are elderly, or if you have alcohol-related problems.

Consumption of alcoholic beverages is not recommended while taking this medicine.

During treatment with antiepileptic medicines such as Gardenale, suicidal thoughts may occur.

If you experience such thoughts at any time, contact your doctor immediately.

Children and adolescents

If a child is to be treated with Gardenale long-term, your doctor will consider prescribing an additional medicine to prevent a bone disease called rickets.

Other medicines and Gardenale

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

The effects of Gardenale may be influenced by, or may influence, the following medicines.

The combination of Gardenale with the following medicines is contraindicated:

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

The combination of Gardenale with the following medicines is not recommended:

• Estrogen-progestins and progestins (hormones used as contraceptives), because Gardenale reduces contraceptive effectiveness. If you are taking Gardenale, you should use a different contraceptive method, such as a barrier method (mechanical contraception) (see section “Pregnancy and breastfeeding”).
• St. John’s wort (Hypericum perforatum), because the effect of Gardenale may be reduced by concomitant administration of St. John’s wort preparations and for at least two weeks after stopping such products. If you are taking St. John’s wort products together with Gardenale, your doctor will monitor you, discontinue therapy with St. John’s wort products, and may adjust the dose of Gardenale.

The combination of Gardenale with the following medicines requires special caution (in some cases, your doctor may adjust the doses):

• Cyclosporine (used to prevent organ transplant rejection), because Gardenale reduces its action.
• Corticosteroids (glucocorticoids, mineralocorticoids, used against inflammation, in certain diseases such as Addison’s disease, and in transplants), because Gardenale reduces their action.
• Doxycycline (antibiotic).
• Saquinavir (antiretroviral medicine), because Gardenale may reduce its efficacy.
• Hydroquinidine, quinidine (used to treat heart problems), because Gardenale reduces their action.
• Levothyroxine (used for thyroid disorders), because your doctor may need to adjust the dosage.
• Theophylline and all theophylline derivatives (used for asthma), because Gardenale reduces its action.
• Folic acid (used for anemias), because it reduces the action of Gardenale.
• Valproic acid (used for seizures), because it increases the action of Gardenale. Gardenale, in turn, reduces the action of valproic acid. Contact your doctor if you experience excessive drowsiness (sedation). Your doctor will perform blood tests to measure concentrations of Gardenale and valproic acid in your blood. Contact your doctor if you experience nausea, vomiting, agitation, confusion, seizures, drowsiness, or coordination problems (symptoms of hyperammonemia).
• Oral anticoagulants (used to thin the blood), because Gardenale reduces their action.
• Imipramine-type antidepressants (used for depression), because they may promote the occurrence of seizures (generalized convulsive seizures).
• Digitoxin (used to treat heart problems), because Gardenale reduces its action.
• Progabide (another medicine for epilepsy), because it increases the action of Gardenale.
• Carbamazepine (used for seizures), because Gardenale reduces its blood levels.
• Disopyramide (used to treat heart problems), because Gardenale reduces its action.
• Other medicines acting on the Central Nervous System (some antidepressants; most antihistamines (anti-H_), benzodiazepines, clonidine and similar medicines, hypnotics, morphine derivatives (analgesics and antitussives), neuroleptics, tranquillizers other than benzodiazepines), because Gardenale increases the effect of these medicines, which may have serious consequences, especially when driving or operating machinery.
• Phenytoin (used for seizures), because Gardenale may alter its blood levels.
• Alprenolol, metoprolol, propranolol (beta-blockers, used to treat high blood pressure and certain heart conditions), because Gardenale reduces their action.

Other combinations to consider:

• Ritonavir, simeprevir, dolutegravir (used against HIV virus and hepatitis C virus), because Gardenale may reduce their action.
• Anticancer drugs, when used together with Gardenale, may result in reduced exposure to these drugs.
• Lamotrigine (used for epilepsy), possible reduction in lamotrigine efficacy and decreased levels of certain blood cells (leukopenia and thrombocytopenia).
• Amitriptyline/amitriptyline oxide (used for depression), possible reduction in their blood concentrations.
• Antithrombotics such as apixaban and ticagrelor (used to prevent blood clots), due to possible reduction in their efficacy.
• Cenobamate, as it may increase phenobarbital blood levels and your doctor may adjust the dose.

Gardenale with food, drinks and alcohol

Avoid consuming alcoholic beverages during treatment with Gardenale.

Pregnancy, breastfeeding and fertility

If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy

Gardenale can cross the placenta. If taken during pregnancy, phenobarbital may cause serious birth defects and developmental delays in the child. Birth defects reported in studies include cleft lip (split upper lip), cleft palate, heart and blood vessel abnormalities, musculoskeletal malformations, and central nervous system abnormalities. Other birth defects have also been reported, such as penile malformations (hypospadias), smaller than normal head size, facial abnormalities, and nail and finger abnormalities.

During pregnancy, your doctor will monitor you for possible fetal malformations.

Women taking phenobarbital during pregnancy have a higher risk than other women of giving birth to a baby with birth defects requiring medical care. In the general population, the baseline risk of major malformations is 2–3%. This risk increases by approximately threefold in women taking phenobarbital.

Babies born to mothers who used phenobarbital during pregnancy may also have an increased risk of being smaller than expected.

Neurological developmental disorders (developmental delays 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, but the risk cannot be ruled out.

If Gardenale is used in combination with other antiepileptic medicines, the risk of adverse effects on the unborn child increases compared to using Gardenale alone.

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 consider the risks and benefits of treatment.

Do not stop taking Gardenale until you have discussed it with your doctor, as abruptly stopping the medicine may increase the risk of seizures, which could harm both you and the unborn child.

If you have taken phenobarbital during the last three months of pregnancy, appropriate monitoring should be performed to detect potential problems in the newborn, such as seizures, excessive crying, muscle weakness, and feeding difficulties.

Since Gardenale reduces levels of a vitamin (folate), your doctor will recommend taking folic acid both before and during pregnancy, even though folic acid reduces the effects of Gardenale (see section “Other medicines and Gardenale”).

Women of childbearing age/Contraception

If you are a woman of childbearing age, you must use an effective contraceptive method during treatment with phenobarbital and for two months after stopping treatment. Phenobarbital may affect how hormonal contraceptives, such as the contraceptive pill, work, making them less effective in preventing pregnancy. Talk to your doctor, who will discuss with you the most appropriate type of contraception to use during phenobarbital treatment.

If you are a woman of childbearing age and planning a pregnancy, consult your doctor before stopping contraception and before starting a pregnancy. Discuss with your doctor the switch to other appropriate treatments to avoid exposing the fetus to phenobarbital.

Newborns

If you take Gardenale, the newborn may experience severe bleeding (hemorrhagic syndrome). Your doctor may prescribe vitamin K during the last month of pregnancy to prevent this.

Breastfeeding

The use of Gardenale during breastfeeding is not recommended because it is excreted in breast milk.

Driving and using machines

Treatment with Gardenale reduces attention and slows reaction time. Take this into account if you intend to drive or operate machinery that requires a high level of alertness due to their potential danger.

3. How to take Gardenale

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is:
Adults
From 100 to 300 mg per day in 2–3 divided doses;
Use in children
From 20 to 100 mg depending on age and weight.
The tablets may be dissolved in a small amount of water or, if necessary, added to food.
Use in the elderly
If you are elderly, your doctor will carefully determine the dosage and may consider reducing the doses indicated above.
If you take more Gardenale than you should
In case of accidental ingestion/overdose of Gardenale, contact your doctor immediately or go to the nearest hospital.
Shortly after taking an excessive dose, symptoms such as nausea, vomiting, headache, confusion, coma accompanied by slowed breathing, obstruction of the trachea and bronchi, and low blood pressure may occur.
If you forget to take Gardenale
Do not take a double dose to make up for a forgotten tablet.
If you stop taking Gardenale
If you have any doubts about using this medicine, consult your doctor or pharmacist; treatment should not be stopped abruptly.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor or pharmacist if you have been taking an antiepileptic medicine for a long time, if you have a history of osteoporosis, or if you are taking medicines called steroids.
If you have been treated with Gardenale during pregnancy, your baby (newborn) may develop, with unknown frequency, a blood clotting disorder characterized by bleeding (hypoprothrombinemia).
For congenital malformations, see section "Pregnancy".

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

• skin allergies (particularly spots and papules resembling measles or scarlet fever),
• learning difficulties (cognitive disorders),
• poor memory (memory deficit),
• abnormal behaviour such as restlessness and aggression,
• nausea and vomiting,
• hand disease characterized by progressive and permanent bending of one or more fingers (Dupuytren's contracture).

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

• loss of coordination of movements (ataxia), especially if you are elderly and taking high doses of Gardenale,
• mood swings,
• sleep disorders/insomnia.

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

• a disease characterized by one or more target-like skin lesions (erythema multiforme),
• skin spots caused by small skin bleedings (purpura),
• excitement, delirium,
• attention disturbance.

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

• Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), whose symptoms may include blisters, peeling or bleeding on any part of the skin (including lips, eyes, mouth, nose, genitals, hands or feet), with or without skin rash. You may also experience flu-like symptoms such as fever, chills or muscle pain,
• drug reaction with eosinophilia and systemic symptoms (DRESS), whose symptoms and signs may include flu-like symptoms and widespread skin rash with high body temperature and swollen lymph nodes. Abnormal blood test results may include increased liver enzyme levels, increased levels of a type of white blood cells (eosinophilia), and swollen lymph nodes,
• acute generalized exanthematous pustulosis (AGEP), whose symptoms may include widespread red, scaly rash with bumps under the skin (including skin folds, chest, abdomen (including stomach area), back and arms) and blisters accompanied by fever at the beginning of treatment,
• severe and widespread reddening with skin peeling (exfoliative dermatitis),
• skin redness with blisters due to the medicine (fixed eruption),
• liver inflammation (toxic hepatitis),
• disorders and reduction, even severe, of blood cells (neutropenia, pancytopenia, aplastic anaemia),
• diseases characterized by a reduction in certain blood cells (leucopenia, agranulocytosis, thrombocytopenia),
• increased size of red blood cells (folate deficiency anaemia) during long-term (chronic) treatment,
• decreased level of consciousness (sedation), involuntary eye movements (nystagmus), mental confusion, especially if you are elderly and taking high doses of Gardenale,
• memory loss (amnesia),
• movement disorder of muscles (dyskinesia),
• in children, hyperactivity symptoms may occur,
• bone diseases, which may present with deformities, pain and fractures, such as osteomalacia (weakening of bone tissue), osteopenia and osteoporosis (thinning of the bones) during long-term (chronic) treatment.

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 at the website
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 Gardenale

Do not store at temperatures above 30°C.
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.
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 Gardenale contains
Gardenale 50 mg tablets

• The active substance is phenobarbital. One tablet contains 50 mg of phenobarbital.
• The other components are: maize starch, magnesium stearate, pregelatinized maize starch.

Gardenale 100 mg tablets

• The active substance is phenobarbital. One tablet contains 100 mg of phenobarbital.
• The other components are: maize starch, magnesium stearate, pregelatinized maize starch.

Description of the appearance of Gardenale and contents of the pack
Gardenale is available as tablets:

• 50 mg tablets: pack of 30 tablets in blister packs
• 100 mg tablets: pack of 20 tablets in blister packs.

Marketing Authorization Holder
Atnahs Pharma Netherlands B.V.
Copenhagen Towers
Ørestads Boulevard 108, 5.tv
DK-2300 Copenhagen S
Denmark

Manufacturer
Sanofi S.r.l.
S.S. 17 km 22 – 67019 Scoppito (AQ)