Consumer medicine information

Dilantin

Phenytoin sodium

BRAND INFORMATION

Brand name

Dilantin

Active ingredient

Phenytoin sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Dilantin.

DILANTIN®

DILANTIN®


 Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.


 1. Why am I taking DILANTIN?

DILANTIN contains the active ingredient phenytoin sodium or phenytoin. DILANTIN is used to control epilepsy. Epilepsy is a condition where you have repeated seizures (fits).

For more information, see Section 1. Why am I taking DILANTIN? in the full CMI.

 2. What should I know before I take DILANTIN?

Do not take if you have ever had an allergic reaction to phenytoin sodium or phenytoin or other hydantoin medicines, methylphenobarbitone or any other barbiturate medicines, other medicines used to treat fits and convulsions or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take DILANTIN? in the full CMI.

 3. What if I am taking other medicines?

Some medicines may interfere with DILANTIN and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

 4. How do I take DILANTIN?

Your doctor will tell you how much medicine to take each day. This may depend on your age, your condition and whether or not you are taking any other medicines. More instructions can be found in Section 4. How do I take DILANTIN? in the full CMI.

 5. What should I know while taking DILANTIN?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using DILANTIN.
  • Tell your doctor immediately if you have any thoughts about suicide or self-harm or have any symptoms of a serious condition affecting your liver.
  • Tell your doctor if you become pregnant while taking DILANTIN.
Things you should not do
  • Do not stop taking DILANTIN and use to treat any other complaints unless your doctor tells you to.
  • Do not give DILANTIN to anyone else, even if they have the same condition as you.
Driving or using machines
  • Be careful driving or operating machinery until you know how DILANTIN affects you.
  • Children should not ride a bike, climb trees or do anything else that could be dangerous if they are feeling drowsy or sleepy.
Drinking alcohol
  • Be careful when drinking alcohol while taking DILANTIN as this can make you more sleepy, dizzy or lightheaded.
Looking after your medicine
  • Keep your tablets/capsules/syrup in a cool dry place where the temperature stays below 25°C.
  • Keep your tablets and capsules in the bottle until it is time to take them.

For more information, see Section 5. What should I know while taking DILANTIN? in the full CMI.

 6. Are there any side effects?

Tell your doctor if you experience these side effects and they worry you: nausea, vomiting, constipation, dizziness, headache, weakness, reduced coordination, confusion, difficulty speaking, sleeplessness or sleepiness, enlarged gums, enlargement of facial features, raised red skin rash. Tell your doctor as soon as possible if you experience unusual changes in mood or behaviour, signs of new or increased irritability or agitation.
Tell your doctor immediately or go to the Emergency Department at your nearest hospital if you experience thoughts about suicide, fever, unusual bruising under the skin, persistent nausea or vomiting, yellowing of the skin and/or eyes, strong stomach pains, more frequent/severe seizures, sudden uncontrollable muscle spasms, sudden signs of allergy, severe skin rash.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.


DILANTIN®

Active ingredient(s): Phenytoin sodium or Phenytoin


 Consumer Medicine Information (CMI)

This leaflet provides important information about using DILANTIN. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking DILANTIN.

Where to find information in this leaflet:

1. Why am I taking DILANTIN?
2. What should I know before I take DILANTIN?
3. What if I am taking other medicines?
4. How do I take DILANTIN?
5. What should I know while taking DILANTIN?
6. Are there any side effects?
7. Product details

1. Why am I taking DILANTIN?

DILANTIN contains the active ingredient phenytoin sodium or phenytoin. DILANTIN belongs to a group of medicines called anticonvulsants. These drugs are thought to work by controlling brain chemicals which send signals to nerves so that seizures do not happen.

DILANTIN is used to control epilepsy. Epilepsy is a condition where you have repeated seizures (fits). There are many different types of seizures, ranging from mild to severe.

DILANTIN is also used to help prevent seizures occurring during or after brain surgery. DILANTIN may be used alone, or in combination with other medicines, to treat your condition. Your doctor may have prescribed DILANTIN for another reason. Ask your doctor if you have any questions about why DILANTIN has been prescribed for you. There is no evidence that DILANTIN is addictive.

2. What should I know before I take DILANTIN?

Warnings

Do not take DILANTIN if:

  • you have an allergy to:
    - phenytoin sodium or phenytoin, the active ingredients in DILANTIN or other hydantoin medicines
    - methylphenobarbitone or any other barbiturate medicines
    - other medicines used to treat fits and convulsions
    - any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction to DILANTIN may include:
    - shortness of breath, wheezing or difficulty breathing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, itching or hives on the skin.
  • you are taking delavirdine, a medicine used in the treatment of HIV infection.
  • packaging is torn or shows signs of tampering.

Always check the ingredients to make sure you can take this medicine.

If you are not sure whether you should start taking DILANTIN, talk to your doctor or pharmacist.

Check with your doctor if you:

  • have allergies to any other medicines, especially barbiturates or any other anticonvulsant medicines, any other substances such as foods, preservatives or dyes.
  • have any other medical conditions
    - liver problems
    - heart problems
    - diabetes
    - high blood sugar levels
    - lymphadenopathy, a condition of the lymph glands
    - Systemic Lupus Erythematosus
    - porphyria, a rare blood pigment disorder
    - hypoalbuminaemia, a decrease in serum albumin in the blood, causing water retention
    - hypersensitivity syndrome, which results in fever, rash, blood disorders and hepatitis
    - a severe skin disorder called Stevens Johnson syndrome
    - toxic epidermal necrolysis, a severe skin reaction with painful red areas, which blister and peel.
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. It is very important to control your fits while you are pregnant. Your doctor can help you decide if it is necessary for you to take DILANTIN during pregnancy. DILANTIN has been known to cause abnormalities and malignancies in the newborns, delaying their growth and causing other harmful side effects.

Talk to your doctor if you are breastfeeding or intend to breastfeed. It is not recommended to breastfeed while taking DILANTIN, as it may pass through breast milk and affect your baby. If you do breastfeed, watch your baby carefully. If your baby develops a skin rash, becomes difficult to wake or has unusual symptoms, don't breastfeed again until you speak to your doctor.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking DILANTIN.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with DILANTIN and affect how it works. These include:

  • disulfiram, a medicine used to treat alcoholism
  • other medicines used to treat fits and convulsions
  • warfarin, a medicine used to prevent blood clots
  • some pain relievers, such as salicylates and tramadol
  • benzodiazepines, medicines used as sleeping tablets, sedatives, tranquillisers, or to treat anxiety and panic attacks
  • medicines used to treat mental illness such as clozapine, phenothiazines
  • medicines used to treat depression
  • medicines used to lower cholesterol
  • corticosteroids such as cortisone and prednisolone
  • ciclosporin, a medicine used to prevent organ transplant rejection and to treat severe rheumatoid arthritis and some severe skin conditions
  • some medicines used to treat cancer
  • some medicines used to treat heart problems
  • some antibiotics and antifungal medicines used to treat infections
  • isoniazid, a medicine used to prevent and treat tuberculosis (TB)
  • antiretrovirals, used in the treatment of HIV infection
  • medicines used to treat parasitic worm infections
  • furosemide, a diuretic (fluid tablet), which is used to reduce water retention and high blood pressure
  • some medicines used to treat stomach or duodenal ulcers, such as omeprazole, sucralfate and cimetidine
  • general anaesthetics and muscle relaxants, medicines used during an operation
  • methadone, a medicine used to control severe pain and to treat heroin addiction
  • methylphenidate, a medicine used to treat Attention Deficit Disorder
  • St John's wort (Hypericum perforatum), an ingredient used in herbal medicines to treat anxiety and depression
  • some medicines used to control diabetes, such as tolbutamide, glibenclamide, chlorpropamide and diazoxide
  • some vitamins such as folic acid and Vitamin D
  • theophylline, a medicine used to treat asthma
  • estrogens, a hormone used in oral contraceptives (birth control pills) and in hormone replacement therapy. Your doctor may advise you to use an additional method of contraception while taking DILANTIN.

These medicines may be affected by DILANTIN or may affect how well it works. Your doctor will tell you if you need different amounts of your medicine, or if you need to take different medicines.

Your doctor and pharmacist may have more information on medicines to be careful with or to avoid while taking DILANTIN.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect DILANTIN.

4. How do I take DILANTIN?

How much to take

  • Your doctor will tell you how much medicine to take each day. This may depend on your age, your condition and whether or not you are taking any other medicines.
  • Your doctor may recommend that you start with a low dose of DILANTIN and slowly increase the dose to the lowest amount needed to control your epilepsy/convulsions.
  • Follow all directions given to you by your doctor carefully. They may differ from the information contained in this leaflet.
  • If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

When to take DILANTIN

  • DILANTIN should be taken at about the same time each day. Taking DILANTIN at the same time each day will have the best effect. It will also help you remember when to take your medicine.
  • Take DILANTIN during or immediately after a meal. This will help prevent stomach upset.

How to take DILANTIN

  • Capsules: swallow whole with at least half a glass of water.
    Infatabs: chew before swallowing.
    Suspension: shake the bottle well and accurately measure the dose with a medicine measure before taking it. Shaking the bottle and using a medicine measure will make sure that you get the correct dose. You can get a medicine measure from your pharmacist.
  • Continue taking DILANTIN for as long as your doctor tells you to. DILANTIN helps control your condition but does not cure it. Therefore, you must take your medicine every day, even if you feel well.
  • Do not stop taking DILANTIN, or lower the dosage, without checking with your doctor. Do not let yourself run out of medicine over the weekend or on holidays.
  • Stopping DILANTIN suddenly may cause unwanted effects or make your condition worse. Your doctor will slowly reduce your dose before you can stop taking it completely.

If you forget to take DILANTIN

DILANTIN should be taken regularly at the same time each day.

If you miss your dose at the usual time and it is almost time for your next dose (within 4 hours), skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose you missed.

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much DILANTIN

If you think that you or anyone else may have taken too much DILANTIN, urgent medical attention may be needed.

You should immediately:

  • phone the Poisons Information Centre
    (Australia telephone 13 11 26) for advice, or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking DILANTIN?

Things you should do

  • Tell any other doctors, dentists, and pharmacists who are treating you that you are taking DILANTIN.
  • If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are taking DILANTIN.
  • Before you have any surgery or emergency treatment, tell your doctor or dentist that you are taking DILANTIN.
  • Tell your doctor if you feel DILANTIN is not helping your condition. Your doctor may need to change your medicine.
  • Tell your doctor if, for any reason, you have not taken DILANTIN exactly as prescribed. Otherwise, your doctor may change your treatment unnecessarily.
  • Tell your doctor if you want to take oral contraceptives while taking DILANTIN. You may need a higher dose of oral contraceptives than usual to prevent pregnancy, or you may need to consider other forms of contraception.
  • If you need to have any medical tests while you are taking DILANTIN, tell your doctor. DILANTIN may affect the results of some tests including test for thyroid function.
  • Be sure to keep all of your doctor's appointments so that your progress can be checked. Your doctor will check your progress and may want to take some tests from time to time. This helps to prevent unwanted side effects.

Call your doctor straight away if you:

  • Notice any of the following
    - increase in seizures (fits)
    - yellowing of the skin and/or eyes
    - swelling of the face
    - strong stomach pains
    - generally feeling unwell with tiredness, weakness and vomiting.
    These symptoms may mean that you have a serious condition affecting your liver. You may need urgent medical attention.
  • If you become pregnant while taking DILANTIN
  • if you have any thoughts about suicide or self-harm, any unusual changes in mood or behaviour, or you show signs of depression.
    Some people being treated with anti-epileptics such as DILANTIN have thoughts of harming or killing themselves.
    Patients and caregivers should be alert and monitor for these effects. Signs and symptoms of suicide include:
    - thoughts or talk of death or suicide.
    - thoughts or talk of self-harm or harm to others
    - any recent attempts of self-harm
    - new or increase in aggressive behaviour, irritability or agitation
    - feelings of depression.
    Mention of suicide or violence must be taken seriously. If you or someone you know is demonstrating these warning signs of suicide while taking DILANTIN, contact your doctor or a mental health professional right away.

Remind any doctor, dentist or pharmacist you visit that you are taking DILANTIN.

Things you should not do

  • Do not give DILANTIN to anyone else, even if their symptoms seem similar to yours or they have the same condition as you.
  • Do not take DILANTIN to treat any other complaints unless your doctor tells you to.
  • Do not stop taking it unless your doctor tells you to.

Things to be careful of

Driving or using machines

Be careful before you drive or use any machines or tools until you know how DILANTIN affects you.

As with other anticonvulsant medicines, DILANTIN may cause dizziness, light-headedness, weakness, tiredness, and decreased coordination in some people.

Children should not ride a bike, climb trees or do anything else that could be dangerous if they are feeling drowsy or sleepy.

DILANTIN may cause drowsiness, dizziness or sleepiness in some people and affect alertness.

Drinking alcohol

Tell your doctor if you drink alcohol.

Be careful when drinking alcohol while taking DILANTIN.

Combining DILANTIN and alcohol can make you more sleepy, dizzy or lightheaded. Your doctor may suggest you avoid alcohol while you are being treated with DILANTIN.

Looking after your medicine

  • Keep your tablets and capsules in the bottle until it is time to take them. If you take the tablets or capsules out of the bottle they will not keep well.
  • Keep your medicine in a cool dry place where the temperature stays:
    - below 30°C (tablets/capsules)
    - below 25°C(syrup)

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Getting rid of any unwanted medicine.

If your doctor or pharmacist tells you to stop taking DILANTIN and you no longer need it or it is out of date, take it to any pharmacy for safe disposal.

Do not take this medicine after the expiry date (EXP) printed on the pack.

6. Are there any side effects?

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking DILANTIN.

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. Sometimes they are serious, most of the time they are not. However, some side effects may need medical attention.

If you are over 65 years of age you may have an increased chance of getting side effects.

If you get any side effects, do not stop taking DILANTIN without first talking to your doctor or pharmacist.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • bleeding, tender or enlarged gums
  • enlargement of facial features including thickening of lips
  • dizziness or light-headedness
  • headache
  • weakness, unsteadiness when walking, reduced co-ordination or slowed reactions
  • forgetfulness, loss of concentration or confusion
  • difficulty speaking or slurred speech
  • sleeplessness or sleepiness
  • nausea (feeling sick) or vomiting
  • constipation
  • aching joints
  • raised red skin rash or itchy skin rash
  • excessive hairiness, especially in women
  • sexual disturbances, such as painful erection
  • tingling or numbness of the hands or feet
  • changes in taste
Speak to your doctor if you have any of these less serious side effects and they worry you.
These are the more common side effects of DILANTIN. Mostly these are mild and short-lived.

Serious side effects

Serious side effectsWhat to do
  • unusual changes in mood or behaviour
  • signs of new or increased irritability or agitation
Call your doctor as soon as possible if you notice any of these serious side effects.
The above list includes serious side effects that may require medical attention.
Very serious side effectsWhat to do
  • thoughts about suicide or self-harm
  • fever, sore throat, swollen glands, mouth ulcers, unusual bleeding or bruising under the skin
  • persistent nausea or vomiting, loss of appetite, generally feeling unwell, fever, itching, yellowing of the skin and/or eyes, dark coloured urine, light coloured bowel motions, pain in the abdomen
  • more frequent or more severe seizures (fits)
  • sudden onset of uncontrollable muscle spasms affecting the eyes, head, neck and body
  • tiredness, headache, shortness of breath when exercising, dizziness or pale skin
  • sudden signs of allergy such as rash, itching or hives, swelling of the face, lips, tongue, throat or other parts of the body, shortness of breath, wheezing or difficulty in swallowing or breathing (anaphylactic reactions)
  • severe skin rash, itching, hives, blisters or peeling skin, which may be accompanied by fever, chills, headache, swollen glands, stomach pain or aching joints and muscles
  • slow heartbeat. You may experience severe fatigue, weakness, sweating or fainting
Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
These are very serious side effects. You may need urgent medical attention or hospitalisation.
These side effects are very rare.

If you are of African or Chinese descent or are immune-deficient you may be at a higher risk of developing some of the above mentioned serious side effects. If you belong to this portion of the population, your doctor will discuss the risks versus the benefits with you.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed above may happen in some people. Some of these side effects (for example, changes in thyroid function, structure of bones, high cholesterol or blood pressure) can only be found when your doctor does blood tests from time to time to check your progress.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What DILANTIN contains

DILANTIN 100 mg capsule

Active ingredient
(main ingredient)

Phenytoin sodium

Other ingredients
(inactive ingredients)
  • lactose monohydrate
  • Confectioner's sugar
    (ARTG PI No.: 1749)
  • purified talc
  • magnesium stearate
  • titanium dioxide
  • sunset yellow FCF
  • erythrosine
  • carbon black
  • gelatin.
Potential allergensLactose and sugars

DILANTIN 30 mg capsule

Active ingredient
(main ingredient)
Phenytoin sodium
Other ingredients
(inactive ingredients)
  • lactose monohydrate
  • Confectioner's sugar (ARTG PI No.: 1749)
  • magnesium stearate
  • purified talc
  • titanium dioxide
  • carbon black
  • gelatin.
Potential allergens

Lactose and sugars

DILANTIN Infatab 50 mg chewable tablet

Active ingredient
(main ingredient)
Phenytoin
Other ingredients
(inactive ingredients)
  • sunset yellow FCF
  • Confectioner's sugar (ARTG PI No.: 1749)
  • quinoline yellow
  • saccharin sodium
  • magnesium stearate
  • purified talc
  • spearmint flavour natural 11584 (ARTG PI No.:1228)
Potential allergensSaccharin and sugars

DILANTIN Paediatric Suspension 30 mg/5 mL oral liquid

Active ingredient
(main ingredient)
Phenytoin
Other ingredients
(inactive ingredients)
  • sodium benzoate
  • sucrose
  • glycerol
  • aluminium magnesium silicate
  • carmellose sodium
  • polysorbate 40
  • vanillin
  • orange flavour 310003E (ARTG PI No.: 10231)
  • ethanol
  • carmoisine
  • sunset yellow FCF
  • citric acid monohydrate
  • hydrochloric acid
  • Imitation Banana Flavour 510120E (ARTG PI No.: 10222)
  • purified water
Potential allergensSugars and benzoates

Do not take this medicine if you are allergic to any of these ingredients.

What DILANTIN looks like

DILANTIN capsules 100 mg - white and orange capsules that are marked PARKE DAVIS on one side and P-D 100 on the other side. They are available in bottles of 200 capsules. (AUST R 295265)

DILANTIN Capsules 30 mg - white capsules marked PARKE DAVIS on one side and P-D 30 on the other side. They are available in bottles of 200 capsules. (AUST R 295264)

DILANTIN Infatabs 50 mg - yellow, chewable, spearmint-flavoured triangular tablets. They are marked P-D 007 on one side and a break bar on the other side. They are available in bottles of 200 tablets. (AUST R 297268) (new formulation)

DILANTIN Paediatric Suspension - a reddish-pink suspension which is available in a 500 mL bottle
(AUST R 14309)

Who distributes DILANTIN

Viatris Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in November 2022.

DILANTIN® is a Viatris company trade mark

DILANTIN_cmi\Nov22/00

Published by MIMS January 2023

BRAND INFORMATION

Brand name

Dilantin

Active ingredient

Phenytoin sodium

Schedule

S4

 

1 Name of Medicine

Phenytoin sodium.
Phenytoin.

2 Qualitative and Quantitative Composition

Dilantin 30 mg capsules: each 30 mg capsule contains 30 mg phenytoin sodium.
Dilantin 100 mg capsules: each 100 mg capsule contains 100 mg phenytoin sodium.
Dilantin Infatabs 50 mg chewable tablets: each 50 mg chewable infatab contains 50 mg phenytoin.
Dilantin 30 mg/5 mL paediatric oral suspension: each 5 mL of paediatric suspension contains 30 mg phenytoin.
Excipients with known effect. Lactose and sugars (30 and 100 mg capsules); saccharin and sugars (chewable tablets); sugars and benzoates (oral suspension).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Capsules 30 mg. Opaque hard gelatin capsule with white body/white lid, marked 'PARKE DAVIS' on one end and 'P-D 30' on the other.
Capsules 100 mg. Opaque hard gelatin capsule with white body/orange lid, marked 'PARKE DAVIS' on one end and 'P-D 100' on the other.
Infatabs 50 mg. Yellow, triangular, spearmint-flavoured chewable tablets with flat sides, bevelled edge, breaking line on one side and 'P-D 007' imprinted on the other.
Paediatric suspension. Reddish-pink suspension.

4 Clinical Particulars

4.9 Overdose

Signs and symptoms. There are marked variations among individuals with respect to phenytoin plasma levels where toxicity may occur. Nystagmus or lateral gaze usually appears at 20 microgram/mL, ataxia at 30 microgram/mL, dysarthria and lethargy appear when the plasma concentration is over 40 microgram/mL, but as high a concentration as 50 microgram/mL has been reported without evidence of toxicity. As much as 25 times the therapeutic dose has been taken to result in a serum concentration above 100 microgram/mL with complete recovery. The lethal dose in children is not known. The lethal dose in adults is estimated to be 2 g to 5 g.
The cardinal initial symptoms are nystagmus, ataxia, dysarthria and CNS depression. Other signs that may be seen are tremor, hyperreflexia, somnolence, drowsiness, lethargy, hallucinations, confusion, mental status changes, slurred speech, blurred vision, nausea, vomiting, choreoathetosis, dyskinesias, hyperglycaemia and mild hypoglycaemia. Severe poisoning may result in respiratory depression. Cardiotoxicity has not been reported with oral overdoses. Irreversible cerebellar dysfunction and atrophy have been reported as a delayed effect following severe overdoses. The patient may become comatose and hypotensive. Bradycardia and asystole/cardiac arrest have been reported (see Section 4.4 Special Warnings and Precautions for Use, Cardiac effects). Death is due to respiratory and circulatory depression.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Pharmacokinetic information. In overdose settings, saturation of the hepatic hydroxylation system occurs and zero order kinetics predominate. Elimination follows a Michaelis-Menten model with a prolonged half-life. As phenytoin is continually excreted, elimination changes from zero order to first order kinetics and drug levels decrease more.
Serial plasma phenytoin concentrations should be monitored. In acute overdose, peak levels are frequently delayed for 24 to 48 hours, and occasionally as long as 7 days.
The proportion of phenytoin in plasma not bound to protein is an important measure of potential toxicity with free phenytoin levels of < 1.5 microgram/mL indicating no signs of toxicity; 1.5 microgram/mL to 5 microgram/mL seen with mild to moderate intoxication; and levels above 5 microgram/mL associated with severe intoxication.
Treatment of overdosage. Treatment is non-specific since there is no known antidote. Most cases of overdosage may be managed conservatively with symptomatic and supportive care. Signs and symptoms of toxicity may persist up to 7 to 10 days after ingestion.
Phenytoin is poorly absorbed in the stomach, therefore, although routine use of activated charcoal is not recommended, it may be considered in the rare patient with a life threatening ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. Administration of a further dose of activated charcoal may be considered in patients with rising serum phenytoin levels or worsening clinical condition despite initial decontamination.
Peritoneal dialysis, diuresis, haemodialysis, plasmapheresis, haemofiltration and total exchange transfusion may be of little benefit although the latter has been used in the treatment of severe intoxication in children.
In acute overdosage the possibility of other CNS depressants, including alcohol, should be borne in mind.
Contact the Poisons Information Centre on 13 11 26 for advice on the management of an overdose.

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Phenytoin was negative in the Ames test and in the in vitro clastogenicity assay in Chinese hamster ovary (CHO) cells. In studies reported in the literature, phenytoin was negative in the in vitro mouse lymphoma assay and the in vivo micronucleus assay in mouse. Phenytoin was clastogenic in the in vitro sister chromatid exchange assay in CHO cells.
Carcinogenicity. In carcinogenicity studies, phenytoin was administered in the diet to mice (10, 25, or 45 mg/kg/day) and rats (25, 50, or 100 mg/kg/day) for 2 years. The incidences of hepatocellular tumors were increased in male and female mice at the highest dose. No increases in tumor incidence were observed in rats. The highest doses tested in these studies were associated with peak serum phenytoin levels below human therapeutic concentrations.
In carcinogenicity studies reported in literature, phenytoin was administered in the diet for 2 years at doses up to 300 ppm (approximately 60 mg/kg/day) and 600 ppm (approximately 160 mg/kg/day) to male and female mice, respectively, and up to 2400 ppm (approximately 120 mg/kg/day) to rats. The incidence of hepatocellular tumors were increased in female mice at all but the lowest dose tested. No increases in tumor incidence were observed in rats. Phenytoin-induced hepatic tumors in mice may be secondary to hepatic enzyme induction in those species and are of uncertain clinical relevance.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Chemical structure. The molecular structure of phenytoin is shown below:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSPHENYT.gif Chemical name: 5,5-diphenylimidazolidine-2,4-dione.
Molecular formula: C15H12N2O2.
Molecular weight: 252.272.
Phenytoin is a white, or almost white, odourless or almost odourless, crystalline powder. It is practically insoluble in water and soluble 1 in 70 alcohol.
Phenytoin sodium is the sodium salt of phenytoin. It is a white, odourless, slightly hygroscopic crystalline powder. It is soluble in water and alcohol.
CAS number. CAS registry number: 57-41-0.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DILANTST.gif