DINTOINALE Coated tablet

Зміст інструкції

1. Dintoinale 100 mg + 40 mg tablets
   1. What Dintoinale is and what it is used for
   2. What you need to know before taking Dintoinale
   3. How to take Dintoinale
   4. Possible side effects
   5. How to store Dintoinale
   6. Contents of the pack and other information

Dintoinale 100 mg + 40 mg tablets

phenytoin sodium + methylphenobarbital

Read this leaflet carefully before taking this medicine as 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Dintoinale is and what it is used for

Dintoinale contains the active ingredients sodium phenytoin and methylphenobarbital.
It belongs to a group of medicines called “antiepileptics” which are used to treat epilepsy.
Sodium phenytoin (a non-hypnotic antiepileptic and therefore without negative effects on mental activity)
acts against convulsions (especially “grand mal”).
Methylphenobarbital acts against convulsions and also has a calming (sedative) effect. The dose
contained in Dintoinale does not cause excessive sedation and therefore allows for good
physical and mental activity.
Dintoinale is used for the treatment of:

• primary generalized epileptic seizures (grand mal)
• partial epileptic seizures, including psychomotor epilepsy when each of the two active ingredients taken separately at adequate doses does not give satisfactory results.

2. What you need to know before taking Dintoinale

Do not take Dintoinale

• if you are allergic to phenytoin, methylphenobarbital or any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to other medicines with a chemical structure similar to the two active ingredients (hydantoin and barbituric products)
• if you suffer from a disease called porphyria
• if you have problems with your liver and kidneys (hepatic and renal insufficiency)
• if you have breathing problems (respiratory insufficiency).

Warnings and precautions
Talk to your doctor or pharmacist before taking Dintoinale:

• if you are elderly, have liver problems or suffer from serious illnesses, as your doctor will prescribe it

an appropriate dosage according to your condition

• if you suffer from a hereditary disorder (an enzyme deficiency) that may alter your body's response to the drug
• if you are taking St. John's Wort preparations (Hypericum perforatum), as if taken simultaneously with Dintoinale, they may decrease its effectiveness (see section “Other medicines and Dintoinale”)
• if you belong to a population of Thai or Chinese ethnicity and are positive for a genetic variant (HLA-B* 1502), as there is a greater risk of developing serious skin side effects
• if you are of Taiwanese, Japanese, Malaysian or Thai origin and tests have shown that you carry the CYP2C9*3 genetic variant.

If Dintoinale is used during pregnancy, there is a risk of harm to the unborn child. Women of
childbearing potential must use effective contraceptive measures during treatment with Dintoinale (see
section “Pregnancy, breastfeeding and fertility”).
Contact your doctor immediately if during treatment with Dintoinale:

• you think about suicide or harming yourself intentionally (a small number of people who have been treated with antiepileptic drugs like Dintoinale have had these thoughts)
• an enlargement of some glands (lymph nodes) occurs, your doctor will prescribe you another medicine against seizures
• you notice the appearance of a rash on the skin characterized by red spots and blisters (exfoliative purpura, or bullous eruption), your doctor will stop the treatment. If, however, the rash is mild (morbilliform or scarlatiniform) the therapy can be resumed after the rash has completely disappeared. If the rash recurs with the resumption of therapy, you must stop treatment. If, in addition to “grand mal” (epilepsy with tonic-clonic seizures) you also suffer from “petit mal” (epilepsy with absence seizures), your doctor will add specific therapy for petit mal.

Life-threatening skin reactions have been reported with phenytoin,
immediately consult your doctor and inform them that you are taking this medicine if you experience the
following reactions:

• Stevens-Johnson syndrome and toxic epidermal necrolysis, which initially appear as round red spots or circular patches often accompanied by blisters on the central trunk. Other signs to look for include ulcers in the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes). These potentially life-threatening skin rashes are often accompanied by flu-like symptoms. These rashes can progress to widespread blisters or skin peeling. The highest risk of developing such skin reactions is evident in the first weeks of treatment. If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis with the use of phenytoin, you should never start treatment again
• DRESS syndrome, which is an allergic reaction to the drug and usually, but not exclusively, presents with fever, rash, enlarged lymph nodes and an increase in a type of white blood cells.

Your doctor will prescribe Dintoinale with caution:

• if you are taking medicines that act on your mind (psychotropic), for pain (analgesics), promote sleep (sedatives, hypnotics), for depression (antidepressants), induce anesthesia (anesthetics), for allergies (antihistamines)
• if you have suicidal tendencies
• if you tend to abuse certain medicines (barbiturates)
• if you are very weak (general state of debilitation)
• if you have lung problems (pulmonary diseases).

Methylphenobarbital, one of the active ingredients of Dintoinale, can lead to habituation (addiction).
If you suddenly stop taking Dintoinale, you may have seizures.
Reducing the dose of Dintoinale, stopping treatment or replacing the medicine
must be done gradually, following your doctor's instructions.

Children
The doctor will check some parameters and assess the possibility of administering vitamin D.

Other medicines and Dintoinale
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
It is particularly important that your doctor is informed if you are taking any of the following
medicines:

• other medicines that act on the mind (psychopharmaceuticals)
• coumarin, blood-thinning medicines (anticoagulants), disulfiram, phenylbutazone, sulfafenazole and isoniazid, as they increase the activity and side effects of sodium phenytoin, one of the active ingredients of Dintoinale
• medicines that act on the nervous system (barbiturates), as they decrease the activity of sodium phenytoin in a variable and unpredictable way
• medicines used to treat depression (tricyclic antidepressants), as at high doses they can promote the onset of seizures. If you are using these medicines, your doctor will prescribe you an appropriate dosage of Dintoinale
• St. John's Wort preparations (Hypericum perforatum), as they may decrease the effect of Dintoinale. The reduction in the effectiveness of Dintoinale may persist for at least 2 weeks after stopping treatment with St. John's Wort products. If you are taking St. John's Wort products simultaneously with Dintoinale, your doctor will prescribe you blood tests and interrupt the therapy with St. John's Wort, and may also prescribe you a different dosage of Dintoinale
• anticoagulants, e.g. rivaroxaban, dabigatran, apixaban, edoxaban
• lacosamide
• ticagrelor
• valproate
• oral contraceptives, as their effectiveness may be diminished by Dintoinale.

The results of some laboratory tests (such as the metopirone test and that of iodine bound to
proteins) may be altered by sodium phenytoin.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding
with breast milk, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy and fertility
If you are of childbearing potential or may become pregnant, your doctor will prescribe the medicine after careful
assessment of the risk-benefit ratio.
If you are planning a pregnancy, your doctor will re-evaluate the need for treatment for epilepsy.
Dintoinale can cause serious birth defects. If you take Dintoinale during pregnancy, the risk
for your baby to develop a birth defect is up to 3 times higher compared to women
who do not take antiepileptic drugs. Serious birth defects have been observed including anomalies
of growth, skull, face, nails, fingers, heart, spinal cord and
spine, penile malformations (hypospadias). Some of these may manifest
together as part of the hydantoin fetal syndrome.
Babies born to mothers who used phenobarbital during pregnancy may also have a higher risk of being smaller than expected.
In children born to mothers who have taken phenytoin and phenobarbital during pregnancy, problems related to neurological development (brain development) have been observed. Some studies have
shown that phenytoin and phenobarbital negatively affect the neurological development
of children exposed in utero to phenytoin and phenobarbital, while other studies have not
found such an effect. The possibility of an effect on neurological development cannot be excluded.
This risk increases if multiple medicines are taken to control seizures.
Therefore, it is important that you take only one medicine for epilepsy, if possible.
If you are a woman of childbearing potential and are not planning a pregnancy, you must use an effective method
of contraception during treatment with Dintoinale and for two months after treatment. Dintoinale can
affect the way hormonal contraceptives work, such as the birth control pill, making them less effective in preventing pregnancy. Talk to your doctor,
who will advise you on the most suitable type of contraception to use while taking Dintoinale.
If you are a woman of childbearing potential and are planning a pregnancy, before stopping
contraception and before starting a pregnancy, talk to your doctor to assess switching to
other appropriate treatments, in order to avoid exposing the fetus to phenytoin and phenobarbital.
Dintoinale should not be used during pregnancy unless nothing else works for you. The
doctor must discuss with you the possible effects of Dintoinale on the unborn child and carefully evaluate the
risks and benefits of treatment.
If you have taken phenobarbital during the last trimester of pregnancy, appropriate monitoring should be performed to detect potential disorders in the newborn, such as seizures, excessive crying, muscle weakness, feeding disorders.
If you are pregnant, or think you may be, you should inform your doctor immediately. You should not
stop taking the medicine until you have spoken to your doctor.
Stopping treatment without consulting your doctor could cause seizures that
could be dangerous for you and the fetus. The doctor may decide to change the
treatment.

Breastfeeding
Sodium phenytoin and methylphenobarbital, the active ingredients of Dintoinale, pass into breast milk.
If you are breastfeeding, your doctor will assess the benefits and risks for the baby.

Driving and operating machinery
Dintoinale can alter reaction times. Keep this in mind if you need to drive any type of vehicle or perform operations that require a normal degree of vigilance.

Dintoinale contains sodium
This medicine contains 8.4 mg of sodium (the main component of table salt) per tablet.
This is equivalent to 0.4% of the recommended daily intake of salt with the diet of an
adult.

3. How to take Dintoinale

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.
If you have previously been treated with other antiepileptic drugs, the switch to Dintoinale
will be done gradually over 6-7 days, with the exception of the medicine Dintoina, which can be replaced
abruptly.
The doctor will choose the optimal dose on a case-by-case basis, through periodic checks of drug levels
in the blood, in order to obtain the maximum therapeutic effect with the minimum of side effects.

Adults
The average dose is 1 tablet at a time, taken regularly during or after each of the 3 meals with
at least half a glass of water.
Rarely, it may be necessary to take a fourth tablet in the evening.
In exceptional cases, it is possible to take up to 5-6 tablets per day.

Children

• Over 6 years of age: 1/2-1 tablet at a time 2-3 times a day, always on a full stomach and with some water (according to the doctor's opinion in relation to age, body weight and severity of the illness).
• Under 6 years of age: 1/2-1 tablet per day, powdered, mixed with jam, sugar or honey and divided into 2-3 doses after meals and with some water.

If you take more Dintoinale than you should
In case of accidental ingestion/taking of an excessive dose of Dintoinale, immediately
inform your doctor or go to the nearest hospital.
In case of overdose, symptoms such as:

• regular, oscillatory and involuntary eye movement (nystagmus)
• tendency to loss of muscle coordination (ataxia)
• drowsiness
• headache
• vomiting
• speech disorders
• mental confusion
• dizziness
• muscle contractions.

If you forget to take Dintoinale
Do not take a double dose to make up for a missed dose.

If you stop taking Dintoinale
Do not suddenly stop taking Dintoinale as it may cause seizures.
Discontinuation of treatment must be done gradually, following your doctor's instructions.
If you have any doubts about the use of 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.
Side effects due to phenytoin sodium, at the recommended doses, are relatively rare.
Rare cases of the following have been reported:

• multiform red spots on the skin (erythema multiforme)
• liver inflammation due to certain substances to which one is exposed (toxic hepatitis)
• decrease in some blood cells (leukopenia, agranulocytosis, thrombocytopenia)
• red spots on the body (purpura)
• excitement
• agitation
• delirium.

The following may also occur:

• hyperactivity in children
• some effects on the stomach and intestines such as nausea, vomiting, heartburn (pyrosis gastrica) and constipation. These effects can be avoided by taking the medicine during or immediately after meals
• problems affecting the blood (agranulocytosis, purpura, thrombocytopenia, leukopenia and pancytopenia). Your doctor will ask you to undergo blood tests
• cases of increased blood cell size (macrocytosis) or production of abnormally shaped blood cells (megaloblastic anemia). In these cases, your doctor will prescribe folic acid
• a reduction in the number of a type of red blood cells (specific red series aplasia) with unknown frequency
• gum swelling, in particular individuals in the case of prolonged treatments with phenytoin sodium. This phenomenon can be avoided or significantly reduced with thorough oral and dental hygiene (repeated several times a day) combined with gentle gum massage and a balanced diet with sufficient calorie and vitamin intake. Daily use of lemon juice or other citrus fruit is recommended
• life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported very rarely
• allergic reaction to the drug, potentially serious, reported with unknown frequency (DRESS syndrome) characterized by skin rash, fever, enlarged lymph nodes and an increase in a type of white blood cells
• bone diseases, including bone thinning (osteopenia and osteoporosis) and fractures. Contact your doctor or pharmacist if you have been on an antiepileptic medicine for a long time, or if you have a history of osteoporosis, or if you are taking medicines called steroids.

Methylphenobarbital is generally well tolerated. Side effects are usually mild and
consist of:

• mild drowsiness
• dizziness
• skin rashes, rarely.

Only at high doses can methylphenobarbital produce:

• drowsiness
• problems with walking (gait disturbances).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through 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 Dintoinale

This medicine does not require any particular storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack. The expiry date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Dintoinale contains

• The active ingredients are phenytoin sodium and methylphenobarbital. Each tablet contains 100 mg of

phenytoin sodium and 40 mg of methylphenobarbital.

• The other ingredients are corn starch, colloidal silica, magnesium stearate, polyvinylpyrrolidone, talc.

Description of the appearance of Dintoinale and contents of the pack
Dintoinale is available in tablet form.
It is available in packs of 30 tablets in blisters.

Marketing authorisation holder and manufacturer
RECORDATI Industria Chimica e Farmaceutica S.p.A. – Via Matteo Civitali, 1 – 20148 Milano.