PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Fenitoina Hikma 50 mg/ml injectable solution

Sodium phenytoin
Equivalent medicinal product
Please read this leaflet carefully before this medicine is administered to you,
it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you personally. Do not give it to others, even if their symptoms are the same as yours, as it could be dangerous.
If you experience any adverse reactions, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4. You may have been given phenytoin as a single dose to control epileptic seizures during an emergency (status epilepticus). In this case, you will only be able to read this patient information leaflet after the medicine has been administered. Your doctor will have considered the important safety information contained in this leaflet, but your urgent need for treatment may have outweighed certain usual precautions. Please review these now, especially if you will continue taking phenytoin.

Contents of this leaflet

What Fenitoina Hikma is and what it is used for
What you need to know before being administered Fenitoina Hikma
How Fenitoina Hikma is administered
Possible side effects
How to store Fenitoina Hikma
Contents of the pack and other information

1. WHAT FENITOIN HIKMA IS AND WHAT IT IS USED FOR

Phenytoin Hikma 50 mg/ml injectable solution contains phenytoin sodium. Phenytoin
sodium belongs to a family of medicines called antiepileptics. Antiepileptics are used
for the prevention and treatment of seizures. This medicine will be administered to you
by a doctor through injection into a vein (intravenously).
Phenytoin Hikma is used for:

The treatment of the following types of seizures:
status epilepticus (a condition characterized by persistent seizures). A persistent seizure is:
a seizure that does not stop, or
a series of seizures accompanied by loss of consciousness
The prevention of seizures occurring during or after neurosurgical procedures (surgery on the brain).

Phenytoin Hikma is not effective in non-convulsive status epilepticus with prolonged absence (a specific type of seizure), or for the prevention or treatment of febrile seizures.

2. WHAT YOU SHOULD KNOW BEFORE BEING ADMINISTERED FENITOIN HIKMA

FENITOIN HIKMA
Do not take Fenitoin Hikma

if you are allergic (hypersensitive) to phenytoin or any other ingredient contained in this medicine (listed in section 6)
if you are allergic (hypersensitive) to other medicines with a similar chemical structure to phenytoin (e.g. hydantoins)
if blood cells and bone marrow are severely damaged
if you have second- or third-degree atrioventricular block (a disorder affecting heart rhythm regulation)
if you have a type of heart disease causing fainting and, sometimes, seizures, known as Stokes-Adams syndrome
if you suffer from sinus bradycardia (slowing of the heartbeat to less than 50 beats per minute), sinoatrial syndrome, or sinoatrial block (disorders affecting heart rhythm regulation)
if you have had a heart attack within the last three months
if you have reduced cardiac output (consult your doctor)
if you are taking medications for HIV infection such as delavirdine

Warnings and precautions
Inform your doctor, pharmacist, or nurse before being administered
phenytoin if you suffer or have previously suffered from any of the following conditions:

Low blood pressure or heart failure
Liver disease, which may require dose adjustment
Diabetes
Porphyria (an inherited disorder affecting haemoglobin biosynthesis)
Heart rhythm disorders (phenytoin may treat some arrhythmias but worsen others)
Alcohol dependence

Take special care with Fenitoin Hikma
A small number of people treated with antiepileptic medicines such as sodium phenytoin
have experienced thoughts of harming themselves or of suicide. If you have ever had
such thoughts, contact your doctor immediately.
Fenitoin Hikma must not be administered in cases of:

heart failure (inability of the heart to pump adequately)
impaired respiratory function
severe hypotension (systolic blood pressure below 90 mm Hg)
heart rhythm disorders such as:
first-degree atrioventricular block
atrial fibrillation
atrial flutter

Fenitoin Hikma must be administered with particular caution if you suffer from:

impaired kidney function
impaired liver function
Your doctor will collect blood and urine samples to monitor liver and kidney function. If you are diabetic, hyperglycaemia (high blood sugar levels) is more likely to occur.

Life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported with the use of phenytoin. These initially appear on the trunk as reddish spots or circular patches, often with blisters at the centre.
Other symptoms to watch for include mouth ulcers, sore throat, nasal ulcers, genital ulcers, and conjunctivitis (red, swollen eyes).
These potentially fatal skin reactions are often accompanied by flu-like symptoms. The rashes may progress to widespread blistering or skin peeling.
The highest risk of such skin reactions occurs during the first weeks of treatment.
If you have previously developed Stevens-Johnson syndrome or toxic epidermal necrolysis while taking phenytoin, you must never restart treatment with phenytoin.
Severe skin reactions may rarely occur during treatment with Fenitoin Hikma. This risk may be associated with a genetic variant in individuals of Chinese or Thai origin. If you are of such origin and have previously tested positive for the genetic variant (HLA-B*1502), discuss this with your doctor before taking phenytoin.
If you develop a rash or other skin symptoms, stop treatment with phenytoin immediately, inform your doctor promptly, and inform them that you are taking this medicine.
Consult your doctor before discontinuing phenytoin. If you stop taking this medicine abruptly, you may experience epileptic seizures.
If you are taking phenytoin concurrently with radiotherapy to the head and the dosage of corticosteroids (a class of medicines) is reduced, you may be more likely to develop a serious skin rash called erythema multiforme or blistering skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see Possible Side Effects in section 4).

Important information regarding treatment
If you have slow hydroxylation
Slow hydroxylation is an inherited disorder that may alter your body's response to the drug. If you have slow hydroxylation, you should therefore exercise caution. Signs of overdose may occur even with moderate doses (see "What to do if you have been given too much Fenitoin Hikma"). In such cases, the dose should be reduced. Your doctor will take a blood sample to check that phenytoin levels are not too high.
If switching to another phenytoin-containing medicine
Other phenytoin-containing medicines may not produce the same phenytoin levels as Fenitoin Hikma. If you switch to another phenytoin medicine, your doctor will monitor you until phenytoin levels return to normal. This may take up to 2 weeks.
If you stop treatment with Fenitoin Hikma abruptly

you may experience more frequent seizures
you may develop status epilepticus (a condition characterised by persistent seizures)

To avoid these problems, your doctor may:

gradually reduce the dose of Fenitoin Hikma
start treatment with the new antiepileptic at a low dose and gradually increase it

If switching to an oral form of phenytoin (e.g. tablets or syrup):
Your doctor will monitor your condition and regularly collect blood samples.
In children, your doctor will also monitor thyroid function.
Based on test results, your doctor will decide whether to modify or discontinue treatment.
If you have low plasma protein levels (hypoproteinaemia), you are more likely to experience nervous system side effects.

Use of Fenitoin Hikma with other medicines
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Some medicines may alter how phenytoin works, or phenytoin may reduce the effectiveness of other medicines taken concurrently. These include:

Medicines used for heart and circulatory problems (e.g. dicumarol, amiodarone, reserpine, digitoxin, digoxin, mexiletine, nisoldipine, furosemide, quinidine, warfarin, and calcium channel blockers including diltiazem and nifedipine)
Medicines used for epilepsy (e.g. carbamazepine, lamotrigine, phenobarbital, sodium valproate, valproic acid, oxcarbazepine, topiramate, succinimides including ethosuximide, and vigabatrin)
Medicines used to treat fungal infections (e.g. amphotericin B, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, miconazole)
Medicines used for tuberculosis and other infections (e.g. chloramphenicol, isoniazid, rifampicin, sulfonamides, sulfadiazine, sulfametizole, sulfamethoxazole-trimethoprim, sulfaphenazole, sulfisoxazole, doxycycline, ciprofloxacin)
Medicines used for gastric ulcers (e.g. omeprazole, sucralfate, and H2 antagonists including cimetidine, ranitidine, famotidine, and some antacids)
Medicines used for asthma and bronchitis (e.g. theophylline)
Medicines used for pain and inflammation (e.g. phenylbutazone, salicylates including aspirin, and steroids)
Medicines used for insomnia, depression, and psychiatric disorders (e.g. chlordiazepoxide, clozapine, diazepam, disulfiram, fluoxetine, methylphenidate, paroxetine, phenothiazines, quetiapine, trazodone, tricyclic antidepressants, fluvoxamine, sertraline, and viloxazine)
Medicines used for diabetes (e.g. tolbutamide)
Some hormone replacement therapies (oestrogens), oral contraceptives (birth control pills)
Medicines used for organ and tissue transplants to prevent rejection (e.g. cyclosporine, tacrolimus)
Medicines used for cancer (e.g. antineoplastic agents including teniposide, fluorouracil, capecitabine, bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate)
Medicines used to reduce high cholesterol and triglyceride levels in the blood (e.g. atorvastatin, fluvastatin, simvastatin)
Medicines used in the treatment of HIV infection (e.g. delavirdine, efavirenz, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir)
Medicines used to eliminate parasitic worms from the body (e.g. albendazole, praziquantel)
Muscle relaxants used during surgery (neuromuscular blockers), certain anaesthetic drugs (halothane), and methadone
Some over-the-counter products (e.g. folic acid, vitamin D)

Your doctor may need to monitor phenytoin blood levels to determine whether any of these medicines are affecting your treatment.
The herbal preparation St John’s wort (Hypericum perforatum)
must not be taken concurrently with this medicine. If you are already taking St John’s wort, consult your doctor before stopping it.
Phenytoin may also interfere with certain laboratory tests you may undergo.

Phenytoin and alcohol
Drinking large amounts of alcohol may also affect phenytoin blood levels.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, or are planning a pregnancy, consult your doctor before being administered Fenitoin Hikma.
Phenytoin should not be administered during pregnancy because it may increase the risk of birth defects. You should remember that oral contraceptives may not be effective while you are taking phenytoin.
If treatment with phenytoin is essential, your doctor will administer the lowest effective daily dose to control your seizures. Pregnancy may also alter the effectiveness of phenytoin, so you may need blood tests and your phenytoin dose may need adjustment.
If you are administered phenytoin to treat your seizures, treatment during pregnancy must not be stopped abruptly, as any sudden interruption or uncontrolled dose reduction may cause seizures to recur, which could harm you and/or your unborn child.
To prevent bleeding in your baby, you should be given vitamin K1 during the last week of pregnancy, and your newborn should receive vitamin K1 after birth.
You must not breastfeed while being administered phenytoin.

Driving and using machines
Phenytoin may cause dizziness or drowsiness. If you experience these symptoms, do not drive or operate any vehicle or machinery and contact your doctor.

Fenitoin Hikma contains ethanol and sodium
This medicinal product contains 10% v/v ethanol (alcohol), i.e. 394 mg per dose, equivalent to 10 ml of beer or 4.17 ml of wine per dose. This may be harmful for individuals suffering from alcoholism.
This information should be considered in pregnant women, breastfeeding women, children, and high-risk groups such as patients with liver disease.
This medicinal product contains less than 1 mmol sodium (23 mg) per glass vial (ampoule). It is essentially "sodium-free".

Fenitoin Hikma contains propylene glycol
It may cause symptoms similar to those caused by alcohol.

3. HOW PHENYTOIN HIKMA IS ADMINISTERED

More detailed information on dosage, use and preparation of Phenytoin Hikma
is provided at the end of this leaflet under the heading “The following information
is intended exclusively for medical or healthcare professionals”.
Phenytoin Hikma will be administered to you by a doctor through slow injection into a vein.
The doctor will determine the required dose and decide when it should be given. The
dose depends on your age, body weight and the condition being treated with Phenytoin Hikma.
While you are receiving Phenytoin Hikma, the doctor will:

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

Duration of treatment
Phenytoin Hikma may be used long-term.
The duration of treatment depends on:

the condition being treated
your response to treatment
your tolerance to side effects (see section 4 “Possible side effects”).

During long-term treatment with Phenytoin Hikma, plasma levels will be monitored so that you receive the lowest effective dose. This will help minimize side effects.
If you think that Phenytoin Hikma is having too strong or too weak an effect, inform your doctor or pharmacist.
If you are given more Phenytoin Hikma than you should
Phenytoin overdose is dangerous. If you think you have been given too much phenytoin, contact your doctor immediately.
If you have any further questions about the use of this medicine, ask your doctor, pharmacist or nurse.
If you are given an excessive amount of Phenytoin Hikma, the following symptoms may occur:
Early symptoms

involuntary rapid eye movements (nystagmus)
cerebellar ataxia (a disorder of movement coordination)
dysarthria (difficulty in articulating speech)

Other symptoms

tremor (shaking)
hyperreflexia (increased reflexes)
drowsiness (slowing down)
exhaustion
lethargy (dullness)
difficulty in articulating speech
diplopia (double vision)
dizziness
nausea
vomiting
coma (loss of consciousness)
pupillary reflex (when the pupil contracts in response to light) may disappear
decreased blood pressure
effects on breathing. These may be fatal.
heart failure. This may be fatal.
irreversible brain damage

If you experience any of these symptoms, inform your doctor immediately. The doctor will take appropriate measures to reduce the excess phenytoin in your body. Your heart and breathing will be monitored and symptoms will be treated.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Contact your doctor immediately if you experience any of the following symptoms after receiving this medicine.

Sudden breathlessness, difficulty breathing, swelling of the eyelids, face or lips, skin rash or itching (particularly if widespread throughout the body). This is more frequently observed in Black patients.
If you experience skin discoloration, swelling and pain at the site of administration that then spreads from the arm to the hands and fingers, this may indicate a condition known as Purple Glove Syndrome. In most cases, this condition resolves spontaneously, but in some cases it may be serious and require urgent medical treatment.
If you develop potentially life-threatening skin rashes causing blisters (which may affect the mouth and tongue). These may be signs of a condition known as Stevens-Johnson Syndrome or toxic epidermal necrolysis (TEN). These conditions have been reported very rarely.
If you notice bruising, fever, paleness or severe sore throat. These may be early signs of a blood disorder, including reduced numbers of red blood cells, white blood cells or platelets. Your doctor may request regular blood tests to monitor for these effects.
Skin rash, fever, swollen glands, increased levels of a type of white blood cells (eosinophilia), and inflammation of internal organs (liver, lungs, heart, kidneys, and large intestine), you may also experience joint pain and inflammation. These may be signs of a hypersensitivity reaction (e.g. drug reaction or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)) or may be due to a condition called systemic lupus erythematosus (SLE).
If you experience confusion or severe mental illness, as this may indicate high levels of phenytoin in your blood. In rare cases, when blood levels of phenytoin remain high, severe and irreversible brain damage has occurred. Your doctor may check your blood levels of phenytoin and may adjust your dose accordingly.

Other adverse reactions that may occur include:

Effects on the nervous system: unusual eye movements, unsteadiness, difficulty controlling movements, tremors, abnormal or uncoordinated movements, slurred speech, confusion, tingling or numbness, drowsiness, dizziness, vertigo, insomnia, nervousness, muscle spasms, headache, and taste disturbances.
Effects on the skin: skin rash, including morbilliform rash, which is generally mild in nature.
Effects on the stomach and intestines: feeling unwell, nausea, vomiting, and constipation.
Effects on blood and lymphatic system: swelling of the lymph glands.
Effects on the liver and kidneys: inflammation of the liver or kidneys, liver damage or liver failure which may be fatal (detectable as yellowing of the skin or whites of the eyes).
Effects on the reproductive system and breasts: changes in the shape of the penis, painful erection.
Effects on hands, face and body: changes in the hands with difficulty straightening the fingers, changes in facial features, enlargement of lips or gums, enlargement or abnormalities of the body or facial hair.
Effects on laboratory tests: increased blood sugar levels or decreased blood levels of calcium, phosphates, folic acid and vitamin D.
Effects on the respiratory system: breathing problems including complete cessation of breathing, inflammation of the lining of the lung.
Effects on the immune system: problems with the body's defense against infections, inflammation of the arterial wall, and immunoglobulin abnormalities.
Effects on the heart and circulation: low blood pressure, dilation of blood vessels. Your blood pressure may drop further and you may experience heart problems if phenytoin is injected into your vein too quickly.
Effects on bones: there have been reports of bone disorders including osteopenia and osteoporosis (thinning of the bone) and fractures. Check with your doctor or pharmacist if you are on long-term antiepileptic treatment, have a history of osteoporosis, or are taking steroids.

Reporting of adverse reactions

If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report adverse reactions directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE FENITOIN HIKMA

Storage of Phenytoin will not be your responsibility.
This medicine does not require any special storage conditions.
The pharmacist will ensure that your medicine is not used after the expiry date stated on the packaging after the word “EXP”. The expiry date refers to the last day of the month. The pharmacist will also ensure that Phenytoin is stored in the original packaging.
Keep Fenitoina Hikma out of the sight and reach of children.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Fenitoina Hikma contains
The active substance is sodium phenytoin.
Each ml of solution contains 50 mg of sodium phenytoin (equivalent to 46 mg of phenytoin).
Each 5 ml vial of injectable solution contains 250 mg of sodium phenytoin (equivalent to 230 mg of phenytoin).
The excipients are:

propylene glycol
ethanol
sodium hydroxide
water for injections

Description of the appearance of Fenitoina Hikma and contents of the pack
Fenitoina Hikma is supplied in clear glass vials.
Fenitoina Hikma is a clear solution.
Pack sizes:
Fenitoina Hikma is available in packs of 5 or 50 vials.
1 vial contains 5 ml of injectable solution.

Marketing Authorisation Holder and Manufacturer
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó n.º 8, 8A and 8B – Fervença
2705-906 Terrugem SNT
Portugal
Tel: ++351-21 960 84 10
Fax: ++351-21 961 51 02

Marketing Authorisation Holder in Italy
Hikma Italia Spa
viale Certosa 10
27100 Pavia

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Germany: Phenytoin Hikma 50 mg/ml Injektionslösung
Italy: Fenitoina Hikma 50 mg/ml Soluzione iniettabile
Poland: Phenytoin Hikma 50 mg/ml Roztwór do wstrzykiwań
Portugal: Fenitoina Hikma
United Kingdom: Phenytoin 50 mg/ml Solution for injection
Romania: Phenytoin Hikma 50 mg/ml Soluţie injectabilă

This leaflet was last reviewed on .

The following information is intended exclusively for medical professionals or healthcare providers:

Method of administration
The injectable solution is intended for intravenous use only, as absorption after intramuscular administration is delayed and unpredictable. Fenitoina Hikma must be injected slowly directly into a large vein via a large-bore needle or intravenous catheter. Subcutaneous or perivascular injection must be avoided, as the alkaline phenytoin injectable solution may cause tissue necrosis.

Use and preparation
The injectable solution must not be mixed with other solutions, as phenytoin may crystallize.
Before use, inspect vials for precipitates or discoloration. The product must not be used if the solution in the vial shows precipitate or turbidity. Phenytoin is suitable for use as long as it remains free from precipitate or turbidity. A precipitate may form if the product has been stored in a freezer. This precipitate will disappear if the vial is allowed to reach room temperature, after which the product will be ready for use.
Only a clear solution must be administered. A slight yellowish tint does not affect the efficacy of the solution.
For single use only. Any unused product must be discarded.
The duration of administration depends on the underlying condition and its course. If the medicine is well tolerated, it may be used indefinitely.

Dosage
The therapeutic range for plasma concentration generally lies between 10 and 20 micrograms/ml of phenytoin; concentrations above 25 micrograms/ml of phenytoin may be within the toxic range.

Status epilepticus and recurrent seizures
Continuous monitoring of ECG, blood pressure, and neurological status, as well as regular determination of plasma phenytoin concentrations, is essential. Additionally, resuscitation equipment must be readily available.

Adults and adolescents over 12 years of age
The initial dose is 1 vial of Fenitoina Hikma (equivalent to 230 mg of phenytoin), administered at a maximum rate of 0.5 ml/min (equivalent to 23 mg of phenytoin per minute). If seizures do not stop after 20–30 minutes, the dose may be repeated.
If seizures cease, a dose of 1 vial of Fenitoina Hikma (equivalent to 230 mg of phenytoin) may be administered every 1.5–6 hours, up to a maximum daily dose of 17 mg/kg body weight (or 6 vials – equivalent to 1380 mg of phenytoin), to achieve rapid saturation.

With a maximum daily dose of 17 mg/kg body weight, this corresponds to:
Body weight Vials Phenytoin
41 kg 3 690 mg
54 kg 4 920 mg
68 kg 5 1150 mg
81 kg 6 1380 mg

Children up to 12 years of age
On Day 1, the maximum daily dose is 30 mg/kg body weight; on Day 2, 20 mg/kg body weight; on Day 3, 10 mg/kg body weight. The maximum infusion rate is 1 mg/kg body weight per minute.

Day 1
With a maximum daily dose of 30 mg/kg body weight, this corresponds to:
Body weight Vials 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
With a maximum daily dose of 20 mg/kg body weight, this corresponds to:
Body weight Vials Phenytoin
12 kg 1 230 mg
23 kg 2 460 mg
35 kg 3 690 mg
46 kg 4 920 mg

Day 3
With a maximum daily dose of 10 mg/kg body weight, this corresponds to:
Body weight Vials Phenytoin
23 kg 1 230 mg
46 kg 2 460 mg

Prophylaxis of seizures
Adults and adolescents over 12 years of age receive 1 to 2 vials of Fenitoina Hikma (equivalent to 230–460 mg of phenytoin) daily, administered at a maximum infusion rate of 0.5 ml/min (equivalent to 23 mg of phenytoin per minute).

Children up to 12 years of age receive 5–6 mg/kg body weight. The infusion rate should be adjusted according to the child's weight and age.

With a daily dose of 5 mg/kg body weight, this corresponds to:
Body weight ml 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

With a daily dose of 6 mg/kg body weight, this corresponds to:
Body weight ml 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 prolonged treatment with Fenitoina Hikma, plasma levels should be monitored, and regular checks (every few weeks) of the full blood count and liver enzyme activity are recommended. Treatment generally need not be discontinued in the presence of stable, mild leukopenia or isolated elevation of gamma-GT.

Osteomalacia (bone fragility) may develop in susceptible patients or those with disorders of calcium metabolism (elevated alkaline phosphatase). Osteomalacia usually responds to vitamin D supplementation.
Therefore, alkaline phosphatase should be monitored regularly.
Additionally, thyroid function should be monitored in children.

Switching to another preparation
Due to the relatively narrow therapeutic range and differing bioavailability among various phenytoin formulations, plasma phenytoin concentrations must be closely monitored when switching from one phenytoin-containing preparation to another. If the dose remains unchanged, steady-state concentrations are expected to be reached after 5–14 days.
Therefore, whenever possible, the dose should be gradually reduced, and the new antiepileptic medicine should be initiated at a low dose, gradually increasing it.
Sudden discontinuation of Fenitoina Hikma may increase seizure frequency or trigger status epilepticus.

Additional information for specific populations

Patients with renal or hepatic impairment
No specific dosage adjustment recommendations are available for this patient group; however, patients with renal or hepatic disease must be treated with caution (see section 4.4). Renal and hepatic impairment require careful monitoring.

Elderly (over 65 years)
As for adults; however, complications may occur more easily in elderly patients.

Neonates
It has been shown that oral absorption of phenytoin in neonates is unreliable. Phenytoin must be administered slowly by intravenous injection at a rate of 1–3 mg/kg/min and at a dose of 15–20 mg/kg. This usually achieves serum phenytoin concentrations within the generally accepted therapeutic range of 10–20 mg/l.

Paediatric population
As for adults. Children tend to metabolize phenytoin more rapidly than adults. This should be taken into account when determining the dosing regimen; therefore, serum level monitoring is particularly useful in these cases.

Management of overdose

Symptoms of overdose
Signs of overdose may occur at different plasma phenytoin levels. Early symptoms include rapid involuntary eye movements, cerebellar ataxia, and dysarthria. Other symptoms may include tremor, hyperreflexia, somnolence, fatigue, lethargy, dysarthria, diplopia, dizziness, nausea, and vomiting. The patient may progress to coma, pupillary reflexes may be lost, and blood pressure may fall. Death may result, for example, from central respiratory depression or circulatory failure. The estimated average lethal dose (acute) in adults is 2–5 g of phenytoin. The lethal dose in paediatric patients is unknown. Overdose may induce irreversible degenerative cerebellar changes.

Treatment of intoxication
Initial treatment should include gastric lavage, administration of activated charcoal, and intensive care monitoring. Haemodialysis, forced diuresis, and peritoneal dialysis are less effective. Experience with the efficacy of activated charcoal haemoperfusion, plasma exchange, and transfusion is insufficient. Therefore, intensive supportive treatment without specific detoxification measures is recommended, along with monitoring of plasma phenytoin levels.