Hidantin absorption is erratic, slow and incomplete from both the gastrointestinal tract and intramuscular injection sites. The half-life is 3–4 h.
What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of Hidantin can be fatal. Overdose symptoms may include twitching eye movements, slurred speech, loss of balance, tremor, muscle stiffness or weakness, nausea, vomiting, feeling light-headed, fainting, and slow or shallow breathing.
What if I forget to take it?
If you take Hidantin and miss a dose:
- once a day - take the missed dose as soon as you remember. If it's less than 12 hours before the next dose is due, it's better to leave out the missed dose and take your next dose as normal.
- twice a day - take the missed dose as soon as you remember. If it's less than 8 hours before the next dose is due, it's better to leave out the missed dose and take your next dose as normal.
Never take 2 doses at the same time. Never take an extra dose to make up for a forgotten one.
If you have epilepsy, it's important to take this medicine regularly. Missing doses may trigger a fit (seizure).
If you forget doses often, it may help to set an alarm to remind you.
You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.
Serious side effects
Very few people taking Hidantin have serious problems.
Tell your doctor straight away if you have a serious side effect, including:
- thoughts of harming or killing yourself - a small number of people taking Hidantin have had suicidal thoughts, which can happen after a few weeks of treatment
- unexpected bruising or bleeding, a high temperature or sore throat - these could be warning signs of a blood disorder
- a high temperature with swollen glands and a skin rash, sometimes with yellowing of your skin or the whites of your eyes, particularly in the first 2 months of treatment - these may be signs of a hypersensitivity reaction, which is more likely to happen if you're black African-Caribbean or have a weakened immune system
- your seizures get worse if you take Hidantin for epilepsy
- a skin rash - this might be a sign of Stevens-Johnson syndrome
How should I take Dilantin?
Take Dilantin exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.
Swallow an extended-release capsule whole and do not crush, chew, break, or open it.
Dilantin Infatabs chewable tablets are not for once-per-day dosing. You must take them 2 or 3 times per day. Follow your doctor's dosing instructions very carefully.
Shake the oral suspension (liquid) before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).
You may need frequent blood tests. You may also need a blood test when switching from one form of Hidantin to another. Visit your doctor regularly.
Tell your doctor if Dilantin does not seem to work as well in controlling your seizures. Do not stop using Dilantin suddenly, even if you feel fine. Stopping suddenly may cause increased seizures. Follow your doctor's instructions about tapering your dose.
In case of emergency, wear or carry medical identification to let others know you have seizures.
Hidantin can cause swelling in your gums. Brush and floss your teeth and visit your dentist regularly to help prevent this problem.
Store at room temperature away from moisture, light, and heat.
Dosage Considerations – Should be Given as Follows:
- Adult: Load 10-15 mg/kg or 15-20 mg/kg at 25-50 mg/min, THEN
- Maintenance: 100 mg intravenously/orally every 6-8 hours as needed
- Administer intravenous (IV) slowly; not to exceed 50 mg/minutes
- Pediatric: 15-20 mg/kg intravenously (IV) in single or divided dose; if necessary may administer additional dose of 5-10 mg/kg 10 minutes after loading dose
- Maintenance: 4-8 mg/kg/day IV divided twice daily
- 100 mg orally three times daily
- Maintenance: 300-400 mg/day; increase to 600 mg/day if necessary
- May adjust dose no sooner than 7-10 day intervals when indicated
- 125 mg orally three times daily, initially
- Increase to 625 mg/day if necessary
- May adjust dose no sooner than 7-10 day intervals when indicated
- Loading dose: 1 g divided into 3 doses (400, 300, 300 mg) administered at 2 hour intervals; initiate dosage 24 hours after loading dose
- Loading dose not for administration to patients with a history of renal or hepaticdisease; reserve for patients who require rapid steady serum levels, when IV administration not desirable, and for patients in a clinic or hospital setting where Hidantin levels can be closely monitored
- Treatment (naive): 100 mg orally three times daily initially
- May adjust dose no sooner than 7-10 day intervals
Therapeutic range: 10-20 mcg/L (total) or 1-2 mcg/L free drug
Immediate action required: Call 999 or go to A&E if:
- you get a skin rash that may include itchy, red, swollen, blistered or peeling skin
- you're wheezing
- you get tightness in the chest or throat
- you have trouble breathing or talking
- your mouth, face, lips, tongue or throat start swelling
You could be having a serious allergic reaction and may need immediate treatment in hospital.
These are not all the side effects of Hidantin.
For a full list, see the leaflet inside your medicines packet.
You can report any suspected side effect to the UK safety scheme.
2.6.1 Interferences in Hidantin Immunoassays
Hidantin (diphenylhydantoin) was first introduced as an anticonvulsant agent in 1938, and it is one of the most widely used anticonvulsant drugs. Immunoassays are used in clinical laboratories for TDM of Hidantin, and in general, these assays are robust, with few reported interferences. One of the potential interferences in immunochemical measurements of Hidantin is cross-reactivity of the major Hidantin metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH) and its glucuronide conjugate with Hidantin immunoassays. HPPH is the primary metabolite of Hidantin, and it is readily conjugated to glucuronide (HPPG), which is excreted in urine. It is estimated that 60–90% of the administered dose of Hidantin can by recovered in the urine as HPPG . This cross-reactivity is particularly important in patients with renal insufficiency because of the increased concentration of metabolites. A 1981 study showed significant interference of metabolites with Hidantin immunoassays . However, newer monoclonal antibody-based immunoassays are less affected by Hidantin metabolites. Tutor-Crespo et al. compared Hidantin concentrations determined by two immunoassays (FPIA and EMIT) with values determined by HPLC for determination of Hidantin using specimens from 36 patients receiving Hidantin. These patients had renal function ranging from normal to severe renal insufficiency (glomerular filtration rate 10–102 mL/min of creatinine clearance). The authors used a deviation of 15% in value as clinically significant, and they concluded that immunoassays provided accurate results in therapeutic monitoring of Hidantin in patients with renal insufficiency . Datta et al. studied the analytical performance of a turbidimetric assay on the ADVIA 1650 analyzer and reported that the Hidantin assay had very low cross-reactivity (5–8%) with the HPPH metabolite and virtually no cross-reactivity with oxaprozin. Oxaprozin interference in some older Hidantin immunoassays had been reported ( Table 2.4 ).
Table 2.4 . Common Interferences in Immunoassays for TCAs
Mechanism of Action
Hidantin primarily acts at the glutamatergic synapse by inhibiting voltage-gated sodium channels (see Fig. 17.2B ). In doing so, Hidantin prevents depolarization of the presynaptic neuron, which in turn inhibits excitatory neurotransmission at the glutamatergic synapse. 19 FosHidantin is a phosphate ester prodrug of Hidantin that can be given parenterally and is associated with fewer infusion-related adverse effects, but it is more expensive. 14
Aside from hypotension, the use of intravenous Hidantin is associated with cardiac rhythm anomalies such as asystole and ventricular fibrillation. Tissue death may occur and may even lead to the formation of gangrene if not managed immediately. Elderly patients may manifest with the purple glove syndrome which is characterized by edema of the distal limbs, discoloration and feeling of pain after intravenous administration. Figure 1 shows the hands of a patient who developed the syndrome .
Getting the most from your treatment
- When you first start a new treatment for epilepsy there may be a change in the number or type of seizures you experience. Your doctor will advise you about this.
- Try to keep your regular appointments with your doctor. This is so your doctor can check on your progress. You will need to have blood tests from time to time.
- While you are being treated for epilepsy there is a small risk that you may develop mood changes, distressing thoughts and feelings about suicide. If this happens, you must tell your doctor about it straightaway.
- People with epilepsy must stop driving at first. Your doctor will advise you about when it may be possible for you to start driving again. This will usually be after a year free of seizures.
- Different formulations and brands of Hidantin can act in a slightly different way in your body. Because of this, it is important that you continue to take Hidantin from the same manufacturer as you have had before. So, each time you collect a prescription, check to make sure your supply looks the same and that the brand name is the same. If you are unsure, or if you have any questions about your prescription, please ask your pharmacist to check it for you.
- If you drink alcohol, ask your doctor for advice. Your doctor may advise you not to drink alcohol while you are on this medicine because it can alter the amount of Hidantin in your body.
- If you buy any medicines, check with a pharmacist that they are suitable for you to take with your antiepileptic medication. Some indigestion remedies can interfere with the amount of Hidantin in your body.
- Many antiepileptic medicines can harm an unborn child. If you are a woman, make sure you have discussed with your doctor which types of contraception are suitable for you and your partner. If you want to have a family, discuss this with your doctor so that you can be given advice from a specialist before you become pregnant.
- You need to take Hidantin regularly every day. Do not stop taking it unless your doctor tells you to stop. Stopping treatment suddenly can cause problems and your doctor will want you to reduce your dose gradually if this becomes necessary.
Before taking Hidantin
Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you (or your child if you are their carer) start taking Hidantin it is important that your doctor knows:
- If you are pregnant, trying for a baby or breastfeeding.
- If you have any problems with the way your liver works.
- If you have a rare inherited blood disorder called porphyria.
- If you have ever had an allergic reaction to a medicine.
- If you are taking any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.
Hidantin induces CYP3A4 activity and is a substrate and inducer of CYP2C9 and CYP2C19. There have been two placebo-controlled studies in healthy men of the pharmacokinetic interaction of voriconazole with Hidantin (46 c ). The first was an open study of the effect of Hidantin 300 mg/day on the steady-state pharmacokinetics of voriconazole 200 mg bd and 400 mg bd. The second was a double-blind randomized study of the effects of voriconazole 400 mg bd on the steady-state pharmacokinetics of Hidantin 300 mg/day. Hidantin reduced the mean steady-state Cmax and AUC of voriconazole by about 50% and 70% respectively; increasing the dose of voriconazole from 200 mg to 400 mg bd compensated for this effect. Voriconazole 400 mg bd increased the mean steady-state Cmax and AUC of Hidantin by about 70% and 80% respectively. Plasma Hidantin concentrations should therefore be monitored and the dose adjusted as appropriate when Hidantin is co-administered with voriconazole.