Aurantin: detailed information

Package leaflet: Information for the user

AURANTIN 250 mg/5 ml injectable solution

Sodium phenytoin
Please read this leaflet carefully before this medicine is administered to you because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult the doctor or the doctor treating your child or the nurse.
If you experience any side effects, including those not listed in this leaflet, consult the doctor or the doctor treating your child or the nurse. See section 4.

Contents of this leaflet:

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

1. What Aurantin is and what it is used for

Aurantin contains the active substance sodium phenytoin, which belongs to a group of medicines called antiepileptics, used for the prevention and treatment of seizures, especially those caused by a brain disorder called epilepsy.
This medicine is indicated:

for the treatment of tonic-clonic epileptic status (grand mal), characterized by an initial phase in which the muscles suddenly become stiff, followed by a second phase in which the muscles begin to contract and relax rapidly, causing convulsions;
for the prevention and treatment of seizures that may occur during or after brain surgery (neurosurgery) and/or in cases of severe brain trauma;
for the treatment of abnormal heart rhythms ( cardiac arrhythmias, such as life-threatening ventricular arrhythmias ), when other therapies (first-line treatments) have proven ineffective, and especially when these disorders (arrhythmias) are caused by medicines that increase the force of heart contraction (digitalis-based medicines).

2. What you should know before Aurantin is administered

Aurantin must not be administered to you or your child:

if you are allergic to sodium phenytoin, to other medicines of a similar type (called hydantoins), or to any of the other ingredients of this medicine (listed in section 6);
by direct injection into an artery (intra-arterial administration);
if you suffer from a slow heart rate (sinus bradycardia);
if you have problems with heart conduction (sinoatrial block, second- or third-degree atrioventricular block);
if you have a condition called Adams-Stokes syndrome, caused by heart problems and characterized by sudden loss of consciousness, often accompanied by seizures;
if you are being treated with a medicine called delavirdine, used for the treatment of AIDS, as this medicine may lose its effectiveness. Generally contraindicated during pregnancy and breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or nurse before Aurantin is administered to you or your child.
For seizure control, Aurantin must be administered to you or your child by intravenous injection (IV route). Administration into a muscle (intramuscular route) is not recommended because the medicine’s effect is slower. Aurantin must not be administered to you or your child via other routes (subcutaneous or perivascular).
Intramuscular administration of Aurantin may cause pain, abscess formation, and necrosis at the injection site.
This medicine may take longer to produce its effects in you or your child than in most people due to genetic factors (polymorphism).
Inform your doctor or your child’s treating physician if you think any of the following conditions apply to you or your child:

you suffer from low blood pressure (hypotension);
your heart is unable to adequately pump blood to the body (severe heart failure);
you have liver function problems (reduced liver function) (see section “Use in patients with liver problems”);
you have severe kidney problems (uremia) (see section “Use in patients with severe kidney problems”);
you have diabetes, as excessive increases in blood sugar levels (hyperglycemia) may occur.

Talk to your doctor, your child’s treating physician, or nurse if you or your child experience any of the following conditions during or after treatment with Aurantin (see also section 4 “Possible side effects”):

suicidal thoughts. During treatment, your doctor will closely monitor you and your child. Immediately inform your doctor if you or your child have thoughts of harming yourself or committing suicide;
serious heart problems, such as cardiotoxic reactions, disturbances in heart rhythm (arrhythmias), reduced heart rate (bradycardia), depression of atrial and ventricular conduction, ventricular fibrillation, sometimes even fatal. These disorders occur especially in elderly and severely ill patients. Heart problems have also occurred in otherwise healthy adults and children without any known heart disease or concomitant illness, following administration of this medicine according to the instructions in this leaflet (e.g., after administration of correct doses and using the recommended infusion rate). For this reason, your doctor will carefully monitor your or your child’s cardiac function (including respiratory function) during administration of Aurantin. If necessary, your doctor will take appropriate measures to prevent or minimize heart problems, including reducing the dose or stopping treatment;
low blood pressure (hypotension), if the medicine is administered too rapidly by intravenous injection (IV route);
irritation and inflammation at the injection site, and in some cases leakage of the medicine from the vein into surrounding tissues;
purple glove syndrome, characterized by swelling due to fluid accumulation (edema), skin discoloration, and pain, even in areas distant from the injection site, when the medicine is administered into a vein in the arm (peripheral injection). These symptoms may appear several days after the injection. In severe cases, tissue damage and tissue death, skin sloughing, may occur, possibly requiring surgical intervention (fasciotomy, skin grafting, or even amputation of the arm);
severe allergic reactions, such as hypersensitivity syndrome (HSS) or drug reaction with eosinophilia and systemic symptoms (DRESS), which may be fatal. Symptoms of these conditions include: fever, skin rash and/or swollen lymph nodes (lymphadenopathy), liver inflammation (hepatitis), kidney inflammation (nephritis), heart inflammation (myocarditis), muscle inflammation (myositis), lung inflammation (pneumonitis), blood disorders such as increased white blood cell count (leukocytosis, eosinophilia), joint pain (arthralgia), enlarged liver (hepatomegaly), yellowing of the skin and eyes (jaundice). Immediately stop treatment with Aurantin and inform your doctor or your child’s treating physician if you experience one or more of these symptoms, as alternative therapy must be initiated. These symptoms, which may appear 2–4 weeks to 3 months after starting treatment, are more common in individuals of African origin, in those who have previously developed these syndromes or have family members affected, and in individuals with severely weakened immune systems (immunosuppressed);
serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which may be fatal. If you or your child develop skin irritation (rashes, eruptions), blistering, or mucosal lesions, inform your doctor immediately, who will decide whether to discontinue treatment and initiate alternative therapy. These effects are more likely to occur:
- during the first weeks of treatment;
- in individuals of African or Asian origin (who may carry the HLA-B*1502 gene);
- if Aurantin is administered concurrently with cranial radiotherapy or corticosteroid therapy;
serious liver problems (hepatotoxicity, liver damage, acute liver failure), sometimes fatal, often associated with severe allergic reactions (HSS/DRESS syndromes). These disorders are more likely in individuals of African origin, those with pre-existing liver disease, and in severely ill or elderly patients. If you or your child develop liver damage, your doctor will permanently discontinue treatment with Aurantin;
serious blood disorders, such as reduced platelet count (thrombocytopenia), reduced white blood cell count (leukopenia, granulocytopenia, agranulocytosis), or reduced counts of all blood cells (pancytopenia), which may be fatal. These disorders may be accompanied by reduced bone marrow activity (bone marrow suppression). In some cases, enlargement and increased number of red blood cells (macrocytosis and megaloblastic anemia) may occur;
swollen lymph nodes (benign lymphadenopathy, pseudolymphoma, lymphoma, Hodgkin’s disease), with or without symptoms of severe allergic reaction (HSS/DRESS syndromes). In this case, inform your doctor or your child’s treating physician immediately, as further evaluations will be needed and the doctor will decide whether to discontinue treatment and initiate alternative therapy;
central nervous system disorders (delirium, psychosis), encephalopathy, worsening of epileptic seizures, and, in severe cases, irreversible brain damage (irreversible cerebellar dysfunction and/or cerebellar atrophy). If you or your child experience symptoms of brain toxicity, inform your doctor immediately, who will order specific tests and assess whether to discontinue therapy. Women of childbearing age who are not planning pregnancy must use effective contraception during treatment with Aurantin.

During treatment with Aurantin, avoid taking medicines containing Hypericum perforatum (St. John’s wort), used for the treatment of depression, as they reduce the effectiveness of phenytoin (see section “Other medicines and Aurantin”).
Laboratory tests
During treatment with Aurantin, your doctor or your child’s treating physician will perform careful and regular blood tests to monitor phenytoin levels, in order to determine the most appropriate dose.
Inform your doctor or your child’s treating physician if you suffer from severe kidney or liver problems, as these conditions may make interpretation of blood test results measuring phenytoin levels difficult.
Elderly patients
If you are over 65 years old, your doctor may administer this medicine at a lower dose than normally recommended or reduce the frequency of administration.
Other medicines and Aurantin
Inform your doctor, your child’s treating physician, or nurse if you or your child are taking, have recently taken, or might take any other medicines.
You or your child will not be given Aurantin if you are already being treated with delavirdine, a medicine used for the treatment of AIDS (see section “Aurantin must not be administered to you or your child”).
Inform your doctor if you or your child are taking any of the following medicines, as it may be necessary to adjust the dose of Aurantin.
Not all medicines are listed below. Speak with your doctor or pharmacist:

analgesics and anti-inflammatory drugs (azapropazone, phenylbutazone, salicylates used to relieve pain and inflammation);
anesthetics (such as halothane, used to induce anesthesia during surgery);
antibacterials (chloramphenicol, erythromycin, isoniazid, sulfadiazine, sulfamethizole, sulfamethoxazole/trimethoprim, sulfaphenazole, sulfisoxazole, sulfonamides, sultamicillin, rifampin, ciprofloxacin, tetracycline, doxycycline, which inhibit or block bacterial growth);
other anticonvulsants (felbamate, oxcarbazepine, sodium valproate, succinimides, topiramate, vigabatrin, carbamazepine, phenobarbital, valproic acid, sodium valproate, lamotrigine, used for seizure control);
antifungal agents (amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole, posaconazole, used to treat fungal infections);
antineoplastic agents (fluorouracil, capecitabine, bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate, teniposide, used in cancer therapy);
benzodiazepines and psychotropic medicines (chlordiazepoxide, diazepam, disulfiram, methylphenidate, trazodone, viloxazine, phenothiazines, used to treat certain mental disorders);
calcium antagonists and cardiovascular agents (amiodarone, dicoumarol, diltiazem, nifedipine, ticlopidine, reserpine, digitoxin, digoxin, mexiletine, nicardipine, nimodipine, nisoldipine, quinidine, verapamil, disopyramide, used to treat high blood pressure and certain heart conditions);
H2-antagonists (cimetidine), proton pump inhibitors (omeprazole), antacids (used to treat stomach disorders);
HMG-CoA reductase inhibitors (fluvastatin, atorvastatin, simvastatin, used to lower blood cholesterol levels);
hormones (estrogens) and oral contraceptives (used to treat menopausal disorders, prevent pregnancy, and/or other female genital disorders); Aurantin may interfere with the action of hormonal contraceptives;
immunosuppressant drugs (tacrolimus, cyclosporine, used to treat immune disorders and after organ transplantation);
oral hypoglycemics (tolbutamide, chlorpropamide, glyburide, used to treat diabetes);
antidepressants (fluoxetine, fluvoxamine, sertraline, clozapine, paroxetine, quetiapine, sertraline, used to treat depression);
antiretrovirals (fosamprenavir, nelfinavir, ritonavir, efavirenz, indinavir, lopinavir, saquinavir, used to treat viral infections);
bronchodilators (such as theophylline, used to treat asthma);
folic acid (used in cases of deficiency of this vitamin, especially during pregnancy);
hyperglycemic agents (diazoxide, which increases blood sugar levels);
anthelmintics (albendazole, praziquantel, used to treat intestinal parasitic infections);
corticosteroids (used to treat inflammation and allergies);
coumarin anticoagulants (such as warfarin, used for certain circulatory disorders);
diuretics (furosemide, which promote urine elimination);
neuromuscular blockers (atracurium, cisatracurium, pancuronium, rocuronium, vecuronium, used to relax muscles during surgery);
opioid analgesics (such as methadone, used to relieve pain and treat drug addiction);
vitamin D (used to restore vitamin levels when they are too low in the body).

During treatment with this medicine, avoid taking St. John’s wort (Hypericum perforatum) products.
Aurantin may alter the results of certain blood tests (iodine-binding proteins, dexamethasone or metyrapone tests, glucose levels, alkaline phosphatase, gamma-glutamyl transferase) and certain tests assessing blood calcium and glucose levels.
Aurantin and alcohol
During treatment with this medicine, avoid drinking alcoholic beverages, as alcohol may alter the effectiveness of phenytoin.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or nurse before this medicine is administered to you.
Pregnancy
If you are pregnant, your doctor will carefully evaluate the risk-benefit ratio before administering this medicine, as Aurantin crosses the placenta and is toxic to the fetus (see “Aurantin must not be administered to you or your child”). Aurantin may cause congenital malformations, tumors, and blood coagulation disorders in the baby. If this medicine is administered during pregnancy, the risk of congenital malformations in the newborn may double or triple compared to normal. The most commonly observed malformations in the baby affect the upper lip (cleft lip), the heart and blood vessels, the part of the embryo from which the central nervous system develops (called the neural tube), and may include growth delays. Effects on the fetus include abnormal facial features and incomplete development of fingers and nails. The risk of congenital malformations increases further if Aurantin is administered together with other similar antiepileptic medicines. Your doctor may perform blood tests to determine the most appropriate dose for your condition.
Breastfeeding
Small amounts of this medicine are excreted in breast milk. If your doctor considers it possible for you to discontinue treatment with Aurantin and breastfeed, your doses will be gradually reduced to prevent new epileptic seizures and serious consequences for you and your baby (see section “If you stop treatment with Aurantin”).
Driving and use of machinery
During treatment with this medicine, driving vehicles or operating machinery is not recommended, as Aurantin may impair reaction times.
Aurantin contains ethanol and sodium
This medicine contains 11% vol ethanol (alcohol), e.g., up to 440 mg per dose, equivalent to 11.2 ml of beer or 4.7 ml of wine per dose.
It may be harmful to alcoholics.
This should be taken into account in pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically “sodium-free”.

3. How to administer Aurantin

This medicine will be administered to you or your child by a doctor or nurse in a hospital or other specialized centre where adequate cardiac resuscitation equipment is available. If you have any doubts, please consult your doctor or nurse.
Aurantin will be administered to you or your child preferably via injection into a vein (intravenous injection) and will be injected slowly.
During administration, your doctor or the doctor treating your child must monitor heart function (electrocardiogram) and blood pressure, and closely observe you, as you may experience severe breathing difficulties (respiratory depression).
In more severe cases, when phenytoin alone is unable to control epileptic seizures, your doctor may decide to administer to you or your child a general anaesthetic normally used during surgical procedures.
More detailed information on dosage, use and preparation of Aurantin is provided at the end of this leaflet under “The following information is intended exclusively for healthcare professionals”.

Use in patients with liver problems
If you or your child have impaired liver function (reduced hepatic function), your doctor or the doctor treating your child may reduce the maintenance dose to prevent excessive accumulation of Aurantin in the body, which could cause serious toxic effects.

Use in patients with severe kidney problems
If you or your child have severe kidney problems (uraemia), your doctor or the doctor treating your child may prescribe the lowest effective dose to control epileptic seizures.

If more Aurantin is administered than prescribed
If you think that you or your child have been given more Aurantin than prescribed, inform your doctor or nurse immediately, as the following symptoms may occur (see also section 4 “Possible side effects”):
rhythmic, involuntary eye movements (nystagmus);
loss of motor coordination (ataxia);
speech disorder (dysarthria);
irreversible brain damage, cerebellar dysfunction and/or cerebellar atrophy;
tremor;
increased reflexes (hyperreflexia);
excessive drowsiness (lethargy);
nausea;
vomiting;
profound unconsciousness (coma);
low blood pressure (hypotension).
In severe cases, these symptoms may lead to death due to respiratory and cardiac arrest (respiratory and circulatory depression). The doctor will take the most appropriate measures depending on your condition.

If you stop treatment with Aurantin
Do not stop treatment abruptly without consulting your doctor, as this may lead to an increase in the frequency of seizures. Any dose reduction, discontinuation of treatment or substitution with another antiepileptic medicine must be carried out exclusively under medical supervision and gradually. If you or your child experience allergic reactions, your doctor may rapidly switch treatment to another medicine not belonging to the same group as Aurantin.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The following side effects may occur:
Very rare (may affect up to 1 in 10,000 people)

Swelling of the lymph nodes (lymphadenopathy, benign lymph node hyperplasia, pseudolymphoma, lymphoma, Hodgkin's disease), which may be accompanied by fever, skin rash (exanthema), and liver problems (hepatic involvement). In such cases, your doctor must monitor you and your baby and may prescribe other medicines to control epileptic seizures.
Reduction in the number of platelets (thrombocytopenia), white blood cells (leukopenia, granulocytopenia, agranulocytosis), or all blood components (pancytopenia). These disorders can sometimes be fatal and may also be associated with loss of bone marrow activity (bone marrow suppression). In some cases, an increase in the size and number of red blood cells (macrocytosis and megaloblastic anaemia) may occur;
Allergic reactions to the medicine (immunological hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (HSS/DRESS) and other disorders of the immune system (systemic lupus erythematosus, nodular periarteritis, immunoglobulin abnormalities);
Severe liver problems (acute liver failure, toxic hepatitis, liver damage);
Vomiting, nausea, constipation (constipation);
Bone fragility (osteopenia, osteoporosis) and increased fracture risk in people who have been taking this medicine for long periods of time.

Not known (frequency cannot be estimated from the available data)

Severe allergic reactions (anaphylactoid reactions and anaphylaxis);
Irritation, inflammation, and pain at the injection site, and in some cases, leakage of the injected solution from the vein;
Tissue damage and death (necrosis, eschar) following inadequate administration (subcutaneous or perivascular injection);
Purple glove syndrome, characterized by swelling due to fluid accumulation (edema), skin discoloration, and pain, even in areas distant from the injection site;
Disturbances in heart rhythm (atrial and ventricular arrhythmias), reduced heart rate (bradycardia), complete cessation of heartbeat (cardiac arrest and death);
Low blood pressure (hypotension), which in severe cases may lead to serious heart and circulation problems (cardiovascular collapse);
Breathing difficulties (respiratory function abnormalities) and, in severe cases, respiratory arrest (respiratory arrest);
Rhythmic and involuntary eye movements (nystagmus), loss of coordination of movements (ataxia), difficulty speaking (dysarthria), and confusion;
Dizziness, altered sensation in different parts of the body (paraesthesia), vertigo, drowsiness, insomnia, transient nervousness, spontaneous muscle contractions (fasciculations), and headache (cephalalgia);
Epileptic seizures characterized by increased muscle tone (tonic seizures);
Movement disorders (dyskinesia, chorea, dystonia, tremors, and akathisia);
Altered taste;
Severe nerve disease (predominantly sensory peripheral neuropathy);
Enlargement of the gums (gingival hyperplasia); more frequent in children or people with poor oral hygiene;
Skin disorders (dermatological manifestations), accompanied by fever and skin irritation (skin rashes similar to scarlet fever or measles);
Severe skin diseases (bullous, exfoliative or purpuric dermatitis, lupus erythematosus, Stevens-Johnson syndrome, and toxic epidermal necrolysis), which may also be fatal;
Phenytoin may cause abnormalities in thyroid function test results.

Reporting of side effects
If you experience any side effects, 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: 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 Aurantin

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and on the vial after "Exp.". The expiry date refers to the last day of that month.
Do not store above 25°C.
Store in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Healthcare professionals know how to properly dispose of unused medicines. This will help protect the environment.

6. Contents of the pack and other information

What Aurantin contains
The active substance is sodium phenytoin.
Each vial contains 250 mg of sodium phenytoin.
The other components are: propylene glycol, ethyl alcohol, sodium hydroxide (see section 2 “Aurantin contains ethyl alcohol and sodium”), water for injections.

Description of the appearance of Aurantin and contents of the pack
Aurantin injectable solution 250 mg/5 ml is available in a box containing 5 vials of 5 ml each.

Marketing Authorization Holder
Pfizer Established Medicine Italy S.r.l.
Via Isonzo, 71
04100 Latina

Manufacturer
Actavis Italy S.p.A.
Viale Pasteur, 10
20014 Nerviano (MI)

The following information is intended exclusively for healthcare professionals

AURANTIN 250 mg/5 ml injectable solution
Sodium phenytoin
DOSAGE AND ADMINISTRATION
Dosage
Treatment of status epilepticus
In patients with continuous epileptic seizures, compared to the more common rapidly recurring seizures such as serial epilepsy, intravenous diazepam is recommended before administering Aurantin due to its rapid onset of action.
After diazepam administration in patients with continuous epileptic seizures and in the initial treatment of serial epilepsy, an initial dose of 10 mg/kg to 15 mg/kg of phenytoin should be administered slowly intravenously at a rate not exceeding 50 mg/minute (this requires approximately 20 minutes in a 70 kg subject). The initial dose should be followed by maintenance doses of 100 mg administered orally or intravenously every 6–8 hours.
Oral absorption of phenytoin in neonates is unreliable; however, an initial intravenous dose of 15 mg/kg to 20 mg/kg of Aurantin produces serum phenytoin concentrations within the generally accepted therapeutic range (10–20 mg/l). The drug must be injected slowly intravenously at a rate of 1–3 mg/kg/minute or at a rate not exceeding 50 mg/minute (whichever is slower).
Monitoring of plasma phenytoin levels is advisable when using Aurantin for the treatment of status epilepticus and for subsequent determination of maintenance dosage. The clinically effective level is usually 10–20 mg/l, although some cases of tonic-clonic seizures may be controlled with lower serum levels.
Phenytoin clearance tends to decrease with increasing age (a 20% reduction in patients over 70 years of age compared to those aged 20–30 years). Phenytoin dosage requirements are highly variable and must be determined on an individual basis.
Intramuscular administration should not be used for the treatment of status epilepticus, as peak plasma levels may take up to 24 hours to be achieved via this route.

Treatment of cardiac arrhythmias
Initially administer a dose of 3.5 mg/kg to 5 mg/kg intravenously. If necessary, repeat the dose once only. The solution must be injected slowly intravenously at a rate not exceeding 1 ml (50 mg) per minute.

Other indications
It is not possible to define a single therapeutic regimen suitable for all other indications. The intravenous route is preferred. Dosages and dosing intervals will be determined according to the individual needs of each patient. Factors such as previous antiepileptic therapy, degree of seizure control, age, and general medical condition must be taken into account. Although absorption of Aurantin is slow when injected intramuscularly, its use by this route may be appropriate in certain conditions.
When short-term intramuscular administration is required in patients previously stabilized on oral phenytoin, appropriate dosage adjustments are essential to maintain therapeutic serum levels. An intramuscular dose 50% higher than the oral dose is necessary to maintain such levels. When switching back to oral therapy, the dose should be reduced by 50% compared to the initial oral dose to avoid excessively high serum levels due to prolonged release from intramuscular injection sites.
In a patient previously untreated with phenytoin, Aurantin may be administered intramuscularly at a dose of 100–200 mg (2–4 ml) every 4 hours as prophylaxis during neurosurgical procedures, continuing for 48–72 hours in the postoperative period.
The dosage should then be gradually reduced to a maintenance dose of 300 mg and adjusted according to serum levels.
If a patient requires intramuscular Aurantin treatment for longer than one week, alternative routes of administration such as gastric intubation should be considered. For periods shorter than one week, upon discontinuation of intramuscular administration, the patient should receive half the initial oral dose for the same duration as the intramuscular treatment with Aurantin. Serum level monitoring is useful to guide appropriate dose adjustment.

Use in the elderly (over 65 years of age): phenytoin clearance is slightly reduced in elderly patients, and lower doses or less frequent administration may be required. However, elderly patients may more easily develop complications.

Use in children: dosage as for adults. However, it has been shown that children tend to metabolize phenytoin more rapidly than adults. This must be taken into account when determining dosages. Monitoring of serum phenytoin levels may be particularly useful in these cases. The drug must be injected slowly intravenously at a rate of 1–3 mg/kg/minute or at a rate not exceeding 50 mg/minute, whichever is slower.

Use in neonates: oral absorption of phenytoin in neonates is inconsistent; however, an intravenous loading dose of 15 mg/kg–20 mg/kg produces serum phenytoin concentrations within the generally accepted therapeutic range (10–20 mg/l). The drug must be injected slowly intravenously at a rate of 1–3 mg/kg/minute.

Method of administration
Rapid infusion may be associated with adverse cardiovascular events (see section 2, Warnings and precautions).
Oral phenytoin should be used whenever possible, due to the risks of cardiac and local toxicity associated with intravenous phenytoin.
For instructions on handling the medicinal product before administration, see section “Precautions for disposal and handling”.

PRECAUTIONS FOR DISPOSAL AND HANDLING
Before administration, parenteral products should be visually inspected for the presence of particulate matter and discoloration, whenever the solution and container permit.
Both the undiluted solution and the infusion mixture may be administered provided they are free from cloudiness and precipitate.
The diluted infusion mixture (phenytoin and saline solution) must not be refrigerated. If undiluted parenteral phenytoin is refrigerated or frozen, precipitation may occur; this should dissolve if the solution is returned to room temperature, and in such case the product may still be used. A slight yellow discoloration may develop. Aurantin must not be mixed with common intravenous infusion solutions, particularly dextrose and dextrose-containing solutions, due to the potential for precipitate formation.
This product is for single use only. After opening, any unused product must be discarded.
Aurantin must be injected slowly directly into a large vein using a large-bore needle or intravenous catheter.
Due to the risk of local toxicity, intravenous phenytoin must be administered directly into a large peripheral or central vein through a large-bore catheter. Before administration, the patency of the intravenous catheter must be tested with physiological saline.
Each intravenous injection of Aurantin must be followed by an injection of sterile physiological saline through the same needle or catheter to avoid local venous irritation due to the alkalinity of the solution.
Continuous infusions must be avoided. Adding Aurantin to intravenous infusion solutions is not recommended due to the probable crystallization of phenytoin.
Continuous monitoring of the electrocardiogram and arterial pressure is essential. Cardiac resuscitation equipment must be available. The patient must be monitored for the development of respiratory depression. If intravenous administration of Aurantin does not terminate the epileptic seizure, other measures, including general anesthesia, should be considered.

For further information, consult the Summary of Product Characteristics.