Phenitoin Hikma

Leaflet accompanying the packaging: Information for the user

Phenytoin Hikma, 50 mg/ml, solution for injection

Active substance: sodium phenytoin

You should read the leaflet carefully before taking the medicine, as it contains important information for you.

• You should keep this leaflet, so you can read it again if you need to.
• You should consult your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If any of the side effects get worse, or if you notice any not listed in this leaflet, please tell your doctor or pharmacist.

Table of contents of the leaflet:

• 1. What Phenytoin Hikma is and what it is used for
• 2. Important information before taking Phenytoin Hikma
• 3. How to take Phenytoin Hikma
• 4. Possible side effects
• 5. How to store Phenytoin Hikma
• 6. Contents of the pack and other information

1. What Phenytoin Hikma is and what it is used for

Phenytoin Hikma, 50 mg/ml, solution for injection contains sodium phenytoin. Sodium phenytoin belongs to a group of medicines called antiepileptic medicines. Antiepileptic medicines are used to prevent and treat epileptic seizures. This medicine is administered by a doctor through intravenous injection.

Phenytoin Hikma is used to:

• treat the following types of epileptic seizures:
• status epilepticus (a state of persistent seizure). Persistent seizure is a seizure that does not stop
• or several seizures between which the patient does not regain consciousness;
• prevent epileptic seizures that occur during or after neurosurgical procedures (brain surgery).

Phenytoin Hikma does not work when there is no status epilepticus (a specific type of seizure) or when it is administered to prevent or treat febrile seizures.

2. Important information before taking Phenytoin Hikma

When not to take Phenytoin Hikma

• if you are allergic to phenytoin or any of the other ingredients of this medicine (listed in section 6),
• if you are allergic (hypersensitive) to other medicines with a similar chemical structure to phenytoin (e.g. hydantoin derivatives),
• if your blood cells and bone marrow are severely damaged,
• if you have a second- or third-degree atrioventricular block (heart rhythm disorders),
• if you suffer from heart disorders (Stokes-Adams syndrome) that cause fainting, and

sometimes seizures;

• if you suffer from sinus bradycardia (slow heart rate - below 50 beats per minute), sick sinus syndrome, or sinoatrial block (heart rhythm disorders),
• if you have had a heart attack in the last three months,
• if you have a low ejection fraction (you should ask your doctor about this),
• Phenytoin Hikma should not be administered subcutaneously, perivascularly during intravenous administration, or intra-arterially due to its high pH.

Warnings and precautions

A small number of people treated with antiepileptic medicines, such as phenytoin, have had thoughts of harming or killing themselves. If such thoughts occur at any time, the patient should contact their doctor immediately.

Phenytoin Hikma should not be administered in cases of:

• heart failure (inability of the heart to pump blood properly),
• respiratory failure,
• severe hypotension (systolic blood pressure below 90 mmHg),
• the following heart rhythm disorders:
• first-degree atrioventricular block,
• atrial flutter,
• atrial fibrillation.

Phenytoin Hikma should be administered with caution if the patient has:

• renal impairment,
• liver impairment. The doctor will order blood and urine tests to monitor liver and kidney function. In diabetic patients, it is more likely that hyperglycemia (high blood sugar) will occur.

When taking Phenytoin Hikma, potentially life-threatening skin changes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Initially, they occur on the torso in the form of a reddish, ring-shaped rash or circular spots, often with centrally located blisters.

Additional symptoms to watch out 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. The rash can progress to generalized blisters or skin peeling. The greatest risk of serious skin reactions occurs in the first few weeks of treatment.

If a patient taking Phenytoin Hikma develops Stevens-Johnson syndrome or toxic epidermal necrolysis, they should never take Phenytoin Hikma again.

Serious skin reactions are rare when taking Phenytoin Hikma. This risk may be associated with a certain gene mutation in patients of Chinese or Thai origin. Patients of such origin who have previously been found to have this gene variant (HLA-B*1502) should discuss this with their doctor before taking Phenytoin Hikma.

If a rash or these skin symptoms occur, Phenytoin Hikma should be discontinued, and the patient should urgently consult a doctor and inform them that they are taking this medicine.

Important information about treatment

Patient with slow hydroxylation

Slow hydroxylation is a hereditary disease. It affects the use of the medicine in the body and the body's reaction to the medicine.

Therefore, patients with slow hydroxylation should be cautious. Symptoms of overdose may occur in them even at moderate doses (see "Taking a higher dose of Phenytoin Hikma than recommended"). In such a case, the dose of the medicine should be reduced. The doctor will order a blood test to check if the phenytoin levels are not too high.

Changing to another phenytoin-containing medicine

After taking other phenytoin-containing medicines, phenytoin levels may be different than after taking Phenytoin Hikma. If the medicine containing phenytoin is changed, the doctor will monitor the patient's condition until the phenytoin levels are stabilized. This may take up to two weeks.

Sudden discontinuation of Phenytoin Hikma

• it is possible that seizures will occur more frequently,
• it is possible that status epilepticus (a state of persistent seizure) will occur.

To avoid these problems, the doctor may:

• gradually reduce the dose of Phenytoin Hikma,
• start taking a new antiepileptic medicine in a small dose and gradually increase it.

Changing treatment to an oral form of phenytoin (e.g. tablets or syrup):

The doctor will monitor the patient's condition and regularly order blood tests.

In the case of children, the doctor will also monitor thyroid function.

The doctor will decide whether any of the test results would indicate the need to change or discontinue treatment.

In patients with low serum protein levels (hypoproteinemia), it is more likely that there will be an adverse effect on the nervous system.

Other medicines and Phenytoin Hikma

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

Many medicines can increase or decrease phenytoin levels in the blood. Phenytoin can change the levels of other medicines in the blood. These effects are called interactions. If it is suspected that the patient is experiencing drug interactions, the doctor will check the phenytoin levels in the patient's blood.

The following substances can increase phenytoin levels:

• alcohol (rapid consumption),
• oral anticoagulants (blood thinners, e.g. dicumarol),
• benzodiazepines (sedatives, e.g. chlordiazepoxide, diazepam, trazodone),
• anesthetics (e.g. halothane),
• other antiepileptic medicines (e.g. sultiam, valproic acid, ethosuximide, mesuximide, felbamate),
• non-steroidal anti-inflammatory medicines (NSAIDs, e.g. salicylic acid, azapropazone, phenylbutazone),
• antibiotics (e.g. chloramphenicol, erythromycin, isoniazid, sulfonamide),
• antifungal medicines (e.g. amphotericin B, fluconazole, ketoconazole, miconazole, itraconazole),
• calcium channel blockers (heart medicines, e.g. amiodarone, diltiazem, nifedipine),
• hormones (e.g. estrogen),
• disulfiram (used to treat alcohol dependence),
• methylphenidate (used to treat attention deficit hyperactivity disorder [ADHD]),
• cimetidine, omeprazole, ranitidine (used to treat stomach ulcers),
• ticlopidine (used to prevent blood clots),
• viloxazine, fluoxetine (antidepressants),
• para-aminosalicylic acid (PAS), cycloserine (used to treat tuberculosis),
• tricyclic antidepressants (e.g. amitriptyline, clomipramine),
• tolbutamide (used to treat diabetes),
• other antiepileptic medicines (e.g. oxcarbazepine, eslicarbazepine acetate and - in some patients - topiramate).

Substances that can decrease phenytoin levels:

• antibiotics (e.g. ciprofloxacin, rifampicin),
• other antiepileptic medicines (e.g. carbamazepine, vigabatrin, phenobarbital, primidone),
• reserpine (used to treat high blood pressure),
• sucralfate (used to treat duodenal ulcers),
• diazoxide (used to treat high blood pressure),
• theophylline (used to treat breathing difficulties),
• long-term excessive alcohol consumption (persistent, long-term alcohol abuse),
• nelfinavir (used to treat viral infections caused by HIV [AIDS]).

Substances that can increase or decrease phenytoin levels:

• antiepileptic medicines (e.g. carbamazepine, valproate, phenobarbital),
• chlordiazepoxide (a sedative),
• diazepam (a sedative).

Valproic acid (an antiepileptic medicine): in patients receiving valproic acid and phenytoin or when increasing the dose of valproic acid, more side effects may occur. In particular, there is a greater likelihood of brain damage (see section 4 "Possible side effects").

Phenytoin can change the levels of the following medicines in the patient's blood and their effects:

• clozapine (used to treat schizophrenia);
• corticosteroids (e.g. dexamethasone, prednisone, fludrocortisone);
• oral anticoagulants (blood thinners, e.g. dicumarol);
• doxycycline, tetracycline (antibiotics);
• praziquantel (used to treat worm infections);
• rifampicin (used to treat tuberculosis);
• itraconazole (an antifungal medicine);
• antiepileptic medicines (e.g. lamotrigine, carbamazepine, valproic acid, felbamate, topiramate, zonisamide or tiagabine and the active metabolite of oxcarbazepine (i.e. MHD) and eslicarbazepine acetate (i.e. eslicarbazepine));
• estrogen (used in hormone replacement therapy [HRT]);
• alcuronium, pancuronium, vecuronium (muscle relaxants);
• cyclosporin (used to prevent rejection of a transplanted organ);
• diazoxide (used to treat high blood pressure);
• furosemide (a diuretic used to treat heart failure);
• paroxetine, sertraline (antidepressants);
• theophylline (used to treat breathing difficulties);
• digoxin (a heart medicine);
• nicardipine, verapamil (used to treat high blood pressure);
• nimodipine (used to prevent cerebral vasospasm);
• quinidine (a heart medicine);
• tricyclic antidepressants (e.g. amitriptyline, clomipramine);
• methadone (used to treat heroin dependence);
• chlorpropamide, glibenclamide (used to treat diabetes);
• tolbutamide (used to treat diabetes);
• vitamin D;
• teniposide (an anticancer medicine);
• oral contraceptives: if you are taking birth control pills, their effect may be uncertain;
• blood thinners (anticoagulants): in patients taking such medicines, it is recommended to regularly check the blood clotting time (INR value);
• methotrexate (an anticancer medicine): the patient may experience:
• a greater number of side effects of methotrexate treatment or
• an increase in methotrexate side effects.
• folic acid: phenytoin may not work effectively when taken with folic acid.

Phenytoin may, when administered with products containing paracetamol, increase the metabolism of paracetamol, which can lead to liver damage.

Pregnancy and breastfeeding

Pregnancy

It should be remembered that birth control pills may not work when taking Phenytoin Hikma.

If you are planning to become pregnant or are already pregnant, you should take Phenytoin Hikma only if your doctor recommends it, after carefully weighing the risks and benefits.

In the case of pregnant women taking any antiepileptic medicine, the risk of birth defects in the fetus is higher (data suggest that this risk is 2-3 times higher). Possible birth defects include:

• hare lip,
• heart defects,
• underdevelopment of fingernails or toes, face,
• neural tube defects (the neural tube is the part of the body from which the nervous system develops),
• growth retardation.

Pregnant women or those planning to become pregnant should discuss this with their doctor immediately. The doctor will check if taking Phenytoin Hikma is necessary.

In case of urgent need to administer Phenytoin Hikma during pregnancy:

• The patient should not, if possible, take other antiepileptic medicines. Taking multiple antiepileptic medicines increases the risk of birth defects.
• Particularly during the first three months of pregnancy, the patient should receive the lowest effective dose. This is the lowest possible dose at which seizures are well controlled. The doctor will decide what this dose should be.
• The patient's and fetus's condition will be monitored:
• Phenytoin levels in the blood serum change during pregnancy and after its completion. The doctor may monitor phenytoin levels in the blood serum to ensure that the patient is receiving the correct dose.
• An ultrasound examination (USG) should be performed. This examination allows for a detailed image of the fetus. The patient should be informed about any problems related to the condition of their child.

During pregnancy, Phenytoin Hikma should not be stopped abruptly. Abrupt discontinuation of treatment may cause seizures to occur. This can be harmful to both the mother and the fetus.

Neonatal care

In the newborn, during the first 24 hours after birth, bleeding may occur. To prevent this:

• In the last week of pregnancy, the doctor should administer a dose of vitamin K1 to the patient;
• The doctor should administer a dose of vitamin K1 to the newborn.

Prevention of folic acid deficiency

To prevent possible folic acid deficiency, the patient should take folic acid during pregnancy. It can be taken in the form of tablets or dietary supplements. The doctor will inform the patient what dose to take. When taking folic acid, the effect of phenytoin may be weaker (see also "Other medicines and Phenytoin Hikma").

Breastfeeding

Small amounts of the active substance (sodium phenytoin) pass into breast milk. It is recommended that the patient does not breastfeed while taking Phenytoin Hikma. However, if the patient wants to breastfeed, the baby should be monitored to ensure that:

• it gains weight properly,
• its need for sleep is not increased.

Driving and using machines

You should not drive vehicles or operate machines, as your ability to drive or operate machines is impaired.

Before driving or operating machines, you should consult your doctor.

Your ability to operate machines or drive may be impaired:

• at the beginning of treatment with Phenytoin Hikma,
• if high doses of the medicine are used,
• when taking this medicine with substances that affect the central nervous system (especially with alcohol).

Important information about some ingredients of Phenytoin Hikma

Phenytoin Hikma contains sodium in an amount of less than 23 mg per glass vial (ampoule). It is almost "sodium-free".

Phenytoin Hikma contains propylene glycol, which can cause symptoms similar to those that occur after consuming alcohol.

This medicinal product contains 10% vol. ethanol (alcohol), i.e. up to 394 mg per dose, which is equivalent to 10 ml of beer, 4.17 ml of wine per dose. This may be harmful to individuals with alcohol dependence.

This should be taken into account in the case of pregnant or breastfeeding women, children, and high-risk patient groups, such as patients with liver disease or epilepsy.

3. How to take Phenytoin Hikma

Detailed information on dosing, handling, and preparation of Phenytoin Hikma is provided at the end of this leaflet under the heading "Information intended only for healthcare professionals".

Phenytoin Hikma will be administered to you by a doctor through slow intravenous injection.

The doctor will decide how much medicine you need and when it should be administered. This depends on your age, weight, and the disease for which you are taking Phenytoin Hikma.

During the administration of Phenytoin Hikma, the doctor will:

• continuously monitor your heart, blood pressure, and nervous system,
• regularly measure phenytoin levels in your blood.

Duration of treatment

Phenytoin can be used for a long time.

The duration of treatment depends on:

• the disease for which you are being treated,
• how well you respond to treatment,
• how well you tolerate side effects (see section 4 "Possible side effects").

During long-term treatment with Phenytoin Hikma, phenytoin levels in the blood serum will be monitored, so that you can receive the lowest effective dose. This will help minimize side effects.

If you feel that Phenytoin Hikma is too strong or too weak, you should talk to your doctor or pharmacist.

Taking a higher dose of Phenytoin Hikma than recommended:

If you receive too high a dose of Phenytoin Hikma, you may experience the following symptoms:

Early symptoms

• involuntary rapid eye movements (nystagmus),
• ataxia (disorder of movement coordination),
• dyarthria (speech impairment).

Other symptoms

• tremors;
• hyperreflexia (exaggerated reflexes);
• drowsiness;
• fatigue;
• lethargy (sluggishness);
• slurred speech;
• double vision;
• dizziness;
• nausea;
• vomiting;
• coma (loss of consciousness);
• possible disappearance of the pupillary reflex (pupils not reacting to light);
• decreased blood pressure;
• breathing difficulties, which can lead to death;
• heart failure, which can lead to death;
• irreversible brain damage.

If you experience any of these symptoms, you should immediately inform your doctor. The doctor will take action to remove excess phenytoin from your body. Your heart and breathing will be monitored, and symptoms will be treated.

4. Possible side effects

Like all medicines, Phenytoin Hikma can cause side effects, although not everybody gets them.

Very common side effects (affecting more than one in ten people):

• nystagmus (involuntary rapid eye movements), ataxia (disorder of movement coordination), paresthesia (tingling sensation), confusion, dizziness of central or peripheral origin, insomnia, headache, increasing irritability, high-frequency tremors at rest, speech disturbances, fatigue, memory and intellectual performance disorders;

Common side effects (affecting up to one in ten people):

• in patients treated for a long time, drowsiness and sedation, perception disorders, and clouding of consciousness or even coma have been reported;
• when administered too quickly intravenously, transient symptoms such as dizziness, vomiting, and dry mouth may occur, which usually resolve within 60 minutes if the patient has not previously taken a phenytoin-containing medicine; in patients treated for a long time, loss of appetite, nausea, vomiting, weight loss, constipation have also been reported;
• erythematous rash;

Uncommon side effects (affecting up to one in 100 people):

• in patients treated for a long time, polyneuropathy (nerve damage) may occur, with a risk of irreversible atrophy of the cerebellum;
• in patients undergoing long-term phenytoin treatment, serious changes in the ECG recording have been reported.

Rare side effects (affecting up to one in 1,000 people):

• it is possible that blood cell count changes may occur, such as leukopenia (decrease in white blood cell count), megaloblastic anemia (formation of very large red blood cells), porphyria (disorders related to certain enzymes that normally participate in the production of porphyrins and heme). If they occur, phenytoin should be discontinued. These symptoms may also gradually resolve if the dose is reduced;
• anaphylaxis and pseudo-anaphylactic reactions have been reported. In rare cases, they can be fatal (this syndrome may include symptoms such as arthralgia, eosinophilia, fever, liver function disorders, lymphadenopathy, or rash);
• laboratory tests should be performed every six months, especially in children, due to the possibility of thyroid function impairment;
• dyskinesia (decreased voluntary movements and occurrence of involuntary movements), athetosis (a condition characterized by involuntary movements), dystonia (muscle contractions and repetitive movements or abnormal postures), tremors, and asterixis (tremors), asystole (flat line on the ECG), conduction block, and suppression of the ventricular escape rhythm in patients with complete atrioventricular block, especially during intravenous administration of phenytoin. It is possible that there will be a proarrhythmic effect in the form of changes or exacerbation of arrhythmias, which can lead to severe cardiac impairment or even cardiac arrest; it is possible that there will be a decrease in blood pressure, exacerbation of existing heart failure, and respiratory failure, especially during intravenous administration. In individual cases, atrial flutter has occurred. Atrial flutter and atrial fibrillation do not resolve after phenytoin administration but may accelerate the ventricular rate due to shortening of the atrioventricular node refractory period;
• in case of liver function disorders with possible involvement of other organs, treatment with phenytoin should be discontinued. These symptoms may also gradually resolve if the dose is reduced. For this reason, during long-term administration of phenytoin, liver enzyme activity should be regularly checked (every few weeks);
• allergic skin rashes (exanthema); severe allergic reactions, such as skin inflammation or exfoliative dermatitis;
• in patients prone to or with calcium metabolism disorders (increased alkaline phosphatase activity), osteomalacia (softening of the bones) may occur. This condition usually responds well to vitamin D administration. For this reason, alkaline phosphatase levels should be regularly checked;
• fever (accompanied by a rash). Local irritation, inflammation, and tenderness have been reported. Local necrosis and exfoliation have been reported after subcutaneous or perivascular injection, which are not recommended routes of administration. Soft tissue irritation and inflammation have occurred at the injection site during intravenous administration of phenytoin, both with and without extravasation.

Very rare side effects (affecting up to one in 10,000 people):

• it is possible that Purple Glove Syndrome, nodular periarteritis (inflammation of medium and small arteries), and immunoglobulin abnormalities may occur;
• excessive growth of gum tissue (gingival hyperplasia), skin changes, such as excessive pigmentation (hirsutism) and hair growth (hypertrichosis), have been reported. Dupuytren's contracture and Stevens-Johnson syndrome and Lyell's syndrome have also been reported. Serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported (see section 4.4);
• muscle weakness (myasthenic syndrome), which resolves after discontinuation of phenytoin.

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

• Purple Glove Syndrome has been reported (a skin condition in which the limbs are swollen, discolored, and painful). If discoloration, swelling, and pain occur at the injection site, which then spread towards the hand and fingers, you should immediately tell your doctor. This may indicate that you have a condition known as Purple Glove Syndrome. In most cases, it resolves spontaneously, but in some cases, it can be severe and requires emergency treatment.

Side effects during long-term treatment

Frequency unknown: (frequency cannot be estimated from available data)

• peripheral sensory polyneuropathy (nerve damage) and tonic seizures,
• irreversible atrophy of the cerebellum (permanent shrinkage of the cerebellum).

During long-term administration of phenytoin (especially when taken orally), encephalopathy (brain damage) may occur. This is particularly likely when other antiepileptic medicines are used concurrently, especially valproic acid.

Symptoms of brain damage include:

Frequency unknown: (frequency cannot be estimated from available data)

• more frequent seizures,
• loss of drive (apathy),
• muscle weakness (decreased muscle tone),
• athetoid dyskinesia (movement disorders),
• severe generalized changes in the brain examination (EEG),
• Bone disorders, including osteopenia and osteoporosis (thinning of bones), and fractures have been reported. During long-term administration of antiepileptic medicines, osteoporosis in the medical history, or taking steroids, you should consult your doctor or pharmacist.

If you experience any side effects, including any possible side effects not listed in this leaflet, you should consult your doctor or pharmacist.

5. How to store Phenytoin Hikma

The medicine should be stored out of sight and reach of children.

Do not use this medicine after the expiry date stated on the carton after "EXP".

The expiry date refers to the last day of that month.

There are no special precautions for storage of the medicinal product.

After first opening the packaging: Phenytoin Hikma should be used immediately.

Do not use the ampoule if the solution in the ampoule is cloudy or contains solid particles.

Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Phenytoin Hikma contains

The active substance of the medicine is sodium phenytoin.

Each ml of solution contains 50 mg of sodium phenytoin (which corresponds to 46 mg of phenytoin).

Each 5 ml ampoule of solution for injection contains 250 mg of sodium phenytoin (which corresponds to 230 mg of phenytoin).

The other ingredients are:

propylene glycol,

ethanol,

sodium hydroxide,

water for injections.

What Phenytoin Hikma looks like and contents of the pack

Phenytoin Hikma is provided in transparent glass vials called ampoules.

Phenytoin Hikma is a clear solution.

Pack sizes:

Phenytoin Hikma is available in packs containing 5 or 50 ampoules.

1 ampoule contains 5 ml of solution for injection.

Marketing authorization holder and manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n.º 8, 8A e 8B – Fervença

2705-906 Terrugem SNT

Portugal

Tel.: ++351-21 960 84 10

Fax: ++351-21 961 51 02

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Germany:

Phenytoin Hikma 50 mg/ml Injektionslösung

Italy:

Phenytoin Hikma 50 mg/ml Soluzione iniettabile

Poland:

Phenytoin Hikma 50 mg/ml Roztwór do wstrzykiwań

Portugal:

Fenitoina Hikma 50 mg/ml Solução injectável

Romania:

Phenytoin Hikma 50 mg/ml Soluţie injectabilă

United Kingdom:

Phenytoin 50 mg/ml Solution for injection

Date of revision of the leaflet

----------------------------------------------------------------------------------------------------------

Information intended only for healthcare professionals or healthcare workers:

Method of administration

The solution for injection is intended for intravenous use only. After intramuscular administration, absorption is delayed and variable. Phenytoin Hikma should be injected slowly directly into a large vein through a large-bore needle or intravenous catheter. Subcutaneous or perivascular injections should be avoided, as the phenytoin injection solution has an alkaline reaction and can cause tissue necrosis.

Handling and preparation

The solution for injection should not be mixed with other solutions, as phenytoin may crystallize.

Before using the ampoule, it should be checked for sediment and discoloration.

The product should not be used if sediment or cloudiness is observed in the solution in the ampoule.

Phenytoin Hikma is suitable for use as long as it does not show cloudiness or sediment. Sediment may form if the product is stored in the refrigerator or freezer. This sediment dissolves if the product is left at room temperature for a while. The product is then suitable for use.

Only a clear solution should be administered. Slight yellow discoloration does not affect the effectiveness of this solution.

For single use only. All unused solution should be discarded.

The duration of treatment depends on the underlying disease and its course. It is unlimited, provided that the medicine is well tolerated.

Dosing

The therapeutic range of phenytoin levels in blood serum is usually between 10 and 20 µg/ml. At phenytoin levels above 25 µg/ml, toxicity symptoms may occur.

Status epilepticus or recurrent seizures at short intervals

It is necessary to monitor the ECG recording, blood pressure, and neurological condition, as well as regularly check the phenytoin level in the blood. Additionally, easy access to a resuscitation kit must be ensured.

Adults and adolescents over 12 years of age:

The initial dose is 1 ampoule of Phenytoin Hikma (corresponding to 230 mg of phenytoin). It is administered at a maximum rate of 0.5 ml/min (corresponding to 23 mg of phenytoin per minute). If the seizure does not resolve after 20-30 minutes, the dose can be repeated.

After the seizures have resolved, 1 ampoule of Phenytoin Hikma (corresponding to 230 mg of phenytoin) can be administered intravenously every 1.5 to 6 hours. The maximum daily dose is 17 mg/kg body weight (or 6 ampoules - corresponding to 1380 mg of phenytoin) to achieve rapid saturation with the medicine.

The maximum daily dose of 17 mg/kg body weight corresponds to:

Body weight

Number of ampoules

Dose of phenytoin

41 kg

3

690 mg

54 kg

4

920 mg

68 kg

5

1150 mg

81 kg

6

1380 mg

Children under 12 years of age

On the first day, the maximum daily dose is 30 mg/kg body weight, on the second day 20 mg/kg body weight, on the third day 10 mg/kg body weight. The maximum rate of intravenous administration is 1 mg/kg body weight per minute.

Day 1

The maximum daily dose of 30 mg/kg body weight corresponds to:

Body weight

Number of ampoules

Dose of phenytoin

8 kg

1

230 mg

15 kg

2

460 mg

23 kg

3

690 mg

31 kg

4

920 mg

38 kg

5

1150 mg

46 kg

6

1380 mg

Day 2

The maximum daily dose of 20 mg/kg body weight corresponds to:

Body weight

Number of ampoules

Dose of phenytoin

12 kg

1

230 mg

23 kg

2

460 mg

35 kg

3

690 mg

46 kg

4

920 mg

Day 3

The maximum daily dose of 10 mg/kg body weight corresponds to:

Body weight

Number of ampoules

Dose of phenytoin

23 kg

1

230 mg

46 kg

2

460 mg

Prevention of seizures

Adults and adolescents over 12 years of age receive 1 to 2 ampoules of Phenytoin Hikma (corresponding to 230 to 460 mg of phenytoin) per day at a maximum administration rate of 0.5 ml/min (corresponding to 23 mg of phenytoin per minute).

Children under 12 years of age receive 5 to 6 mg/kg body weight. The administration rate is reduced according to the child's body weight and age.

The daily dose of 5 mg/kg body weight corresponds to:

Body weight

ml

Dose of phenytoin

9 kg

1

46 mg

18 kg

2

92 mg

28 kg

3

138 mg

37 kg

4

184 mg

46 kg

5

230 mg

The daily dose of 6 mg/kg body weight corresponds to:

Body weight

ml

Dose of phenytoin

8 kg

1

46 mg

15 kg

2

92 mg

23 kg

3

138 mg

31 kg

4

184 mg

38 kg

5

230 mg

46 kg

6

276 mg

During long-term administration of Phenytoin Hikma, it is necessary to regularly (every few weeks) monitor phenytoin levels in the blood serum and check the morphology and liver enzyme activity. A morphology result indicating moderate, stable leukopenia or isolated elevated GGT usually does not require discontinuation of treatment.

In patients prone to or with calcium metabolism disorders (increased alkaline phosphatase activity), osteomalacia (softening of the bones) may occur. This condition usually responds well to vitamin D administration. For this reason, alkaline phosphatase levels should be regularly checked.

In addition, in children, thyroid function should be monitored.

Changing medicines

Due to the relatively narrow range of therapeutic phenytoin levels in the blood serum and the different bioavailability of different medicinal products, when changing the medicine to another phenytoin-containing product, its level in the blood serum should be closely monitored. Achievement of a steady state (constant level in the blood serum) can be expected after administration of a constant dose of the medicine for a period of 5 to 14 days.

For this reason, the dose of the product should be (if possible) gradually reduced, and new antiepileptic medicines should be introduced starting from a small dose, gradually increased. In case of sudden discontinuation of Phenytoin Hikma, it may lead to an increase in the frequency of seizures or status epilepticus.

Additional information for specific patient groups

Patients with renal/hepatic impairment:

There is no reference to dose adjustment in this patient group, but caution should be exercised in patients with kidney and liver diseases (see section 4.4). Renal and hepatic impairment require careful monitoring.

Elderly patients (over 65 years of age):

As for adults. In elderly patients, complications may occur more frequently.

Newborns:

It has been shown that the absorption of phenytoin after oral administration is uncertain. Phenytoin Hikma should be injected slowly intravenously at a rate of 1-3 mg/kg/min in a dose of 15-20 mg/kg. This usually allows achieving phenytoin levels in the serum within the generally accepted therapeutic range of 10-20 mg/l.

Infants and children:

As for adults. Phenytoin metabolism in children is often faster than in adults. This should be taken into account when determining the dosing regimen. In such cases, monitoring of serum levels is particularly beneficial.

Treatment of Overdose Overdose Symptoms

Overdose symptoms may occur in individuals with different phenytoin serum concentrations. Early
symptoms include involuntary, rapid eye movements, cerebellar ataxia, and dysarthria. Additional symptoms
may include: tremors, hyperreflexia, drowsiness, exhaustion, lethargy, slurred speech, diplopia,
dizziness, nausea, vomiting. The patient may lapse into a coma, pupillary reflexes may disappear, and arterial
pressure may drop. Death is caused by, for example, central respiratory depression or circulatory failure.
It is estimated that the average lethal dose (with single administration) is 2–5 g of phenytoin in adults.
The lethal dose in children and adolescents is unknown. Overdose can lead to irreversible degenerative
changes in the cerebellum.
Treatment of Poisoning
Preliminary treatment must include gastric lavage, administration of activated charcoal, and monitoring
of the patient in the intensive care unit. Hemodialysis, forced diuresis, and peritoneal dialysis are less
effective. There is a lack of relevant experience regarding the effectiveness of hemoperfusion with activated
charcoal, total plasma exchange, and blood transfusion. For this reason, intensive internal treatment should
be carried out without special detoxification procedures, but phenytoin serum concentrations should be
monitored.