What Are Appropriate Phenytoin Levels?

Phenytoin is an antiepileptic drug. This product is a class IB antiarrhythmic drug, which has membrane stability and inhibits fast sodium ion influx.

On October 27, 2017, the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization initially compiled the reference, and phenytoin was included in the list of 2B carcinogens. ^[1]

Chinese name: Phenytoin
Foreign name: Phenytoin

Molecular formula: C15H12N2O2
Molecular weight: 252.27

Phenytoin Basic Information

CAS number: 57-41-0

Properties: white powder

Melting point: 293-295 ° C

Water solubility: <0.01 g / 100 mL at 19 ° C.

Phenytoin pharmacological action

Its membrane effect is related to extracellular potassium ion concentration, myocardial state, and blood drug concentration. When the extracellular potassium concentration is low, the low-concentration drug increases the maximum rate of 0 phase division and the action potential amplitude, accelerates conduction, and is beneficial to eliminate digitalis poisoning. Arrhythmia with hypokalemia and reentrant arrhythmia due to one-way block. When the extracellular potassium concentration is normal or elevated, high-concentration drugs have an inhibitory effect, but are significantly lower than those of other antiarrhythmic drugs. This product shortens the action potential interval and the effective refractory period, but the former shortens it more significantly, so the effective refractory period is relatively prolonged, which is beneficial to eliminate arrhythmia caused by reentrant agitation. This product may also inhibit calcium influx, which is different from the antiarrhythmic effect of other local anesthetics. In addition, it can reduce myocardial autonomy, suppress sympathetic centers, reduce their outgoing impulse, and increase atrial fibrillation and ventricular fibrillation thresholds. The above effects have a greater impact on the ventricle than the atrium. It has little effect on the electrocardiogram, can shorten the PR and QT intervals, and has no effect on QRS waves. Can reduce the contractility of the original heart disease. Intravenous medication can dilate peripheral blood vessels.

Phenytoin kinetics

Oral absorption is slow, 85 to 90% is absorbed by the small intestine, and the absorption is very poor in newborns. Intravenous absorption is fast; intramuscular absorption is incomplete and irregular, and the peak dose is only 1/3 of oral administration. The bioavailability of the oral tablet is about 75%, and it is distributed in the intracellular and extracellular fluids after absorption, and there may be more intracellular than extracellular. The protein binding rate is very high, ranging from 88 to 92%. It mainly binds to albumin, and the protein binding in brain tissue may be slightly higher.

The oral drug concentration reached a peak in 4 to 12 hours. The effective blood concentration was 10 to 20 g / ml, and the steady-state concentration was reached at about 7 to 10 times per day at 300 mg. Oral drug concentrations exceeding 20 g / ml were prone to toxic reactions. Occurrence of nystagmus, ataxia in excess of 30 g / ml, and severe toxicity in excess of 40 g / ml. The average half-life of phenytoin is 22 hours, but the range of variation is large (7 to 42 hours). The half-life of patients taking long-term phenytoin can vary from person to person, depending on concentration, and can range from 15 to 95 hours, or even longer. It is mainly metabolized in the liver, and the metabolites have no pharmacological activity. Among them, hydroxyphenytoin (about 50 to 70%) is mainly excreted through the kidneys and alkaline urine is excreted faster. After a certain dose of the drug is used, the metabolic capacity of the liver reaches saturation. At this time, even if a small dose is added, the blood concentration will easily increase disproportionately, and a toxic reaction will occur. It is a typical drug of zero order pharmacokinetics. When the drug concentration is low, it is appropriate to increase the dose by 50 mg per day. When the blood drug concentration reaches 15 g / ml, it is appropriate to increase the dose by 25 mg per day. After increasing the dose, it should be observed for 2 to 3 weeks to reach the new steady-state blood concentration. Because the half-life at this time becomes longer, the time to reach the steady-state concentration is also prolonged, and the pseudo-steady-state phenomenon can be avoided.

Phenytoin indications

It is suitable for the treatment of systemic tonic-clonic seizures, complex partial seizures (psychomotor seizures, temporal lobe epilepsy), simple partial seizures (localized seizures), and persistent epilepsy. It can also be used for the treatment of trigeminal neuralgia, recessive dystrophic bullous epidermolysis (recessivedystrophicepidermolysisbullosa), episodic choreography, episodic dance disorders, and behavioral disorders such as anger, anxiety, and insomnia with hyperexcitability. ), Myotonia and cardiac conduction disorders when tricyclic antidepressants are overdose. Phenytoin does not control minor episodes of absence. If accompanied by an absence episode, other drugs should be combined.

The following is a description of the antiarrhythmic effect of phenytoin sodium: it is mainly applicable to ventricular and supraventricular arrhythmias caused by digitalis poisoning. Flutter well). It is less effective against a variety of other causes of arrhythmia, including arrhythmias combined with prolonged QT interval, ventricular arrhythmias after electrical conversion, and intraoperative and postoperative (especially postoperative congenital heart disease combined with cardiac effort) (Failure), catheter examination, contrast injection and general anesthesia caused by ventricular arrhythmia and lidocaine ineffective or unusable.

Phenytoin dosage

Anti-epileptic:

1. Oral adult dosage: 250-300mg daily, 100mg at the beginning, 2 times a day, 250-300mg daily in 1-3 weeks, divided into 3 times, but due to the characteristics of individual differences and saturation kinetics, Medication needs to be individualized. After the split application reaches the control and the blood concentration reaches a steady state, it may be considered to switch to a long-acting preparation once. If the onset is frequent and the therapeutically effective blood drug concentration needs to be reached quickly, the dose of 12-15 mg / kg can be divided into 2-3 doses, once every 6 hours, and 100 mg (or 1.5-weight) can be given the next day. 2mg / kg), 3 times a day until adjusted to the appropriate dose. When used as a collagenase synthesis inhibitor, first use it twice daily at a weight of 2-3mg / kg, and increase it to a dose that the patient can tolerate within 2-3 weeks. The blood concentration reaches at least 8g / ml. Generally 100-300mg daily.

Commonly used amount in children: Take 2-3 times daily at the beginning at 5mg / kg of body weight, and adjust it as needed later, taking no more than 250mg per day as the degree. The maintenance amount is 4 to 8 mg / kg or 250 mg / m2 of body surface area, divided into 2 to 3 doses per day. If conditions permit, follow-up observation can be made under blood concentration monitoring.

2. Intravenous injection commonly used in adults: anticonvulsant, 150-250mg, not more than 50mg per minute, 30-minutes can be injected intravenously again after 30 minutes, the total daily amount does not exceed 500mg. In elderly, severely ill and patients with impaired liver function, the intravenous injection volume should be reduced, and the injection rate should be slowed down to 50 mg every 2-3 minutes to avoid adverse or toxic reactions.

Commonly used amount in children: when anticonvulsant, intravenous injection of 5mg / kg according to body weight or body surface area of 2S0mg / m2, one or two injections.

(1) Those who are allergic to one of the hydantoin drugs may also be allergic to other medicines of the same family, such as metformin and phenytoin.

(2) There are reports of carcinogenesis, including taking during pregnancy, and children with neuroblastoma after delivery.

(3) This product can pass through the placenta. Although the relationship with teratogenicity is unknown, the advantages and disadvantages should be considered. The vast majority of women with epilepsy still give birth to normal infants, but there are reports that congenital abnormalities in infants include rabbit lips, cleft palate, cardiac abnormalities and "fetal phenytoin syndrome" (prenatal growth defects, Microcephaly, craniofacial abnormalities, nail dysplasia and mental developmental defects) are more common. As to whether these teratogenicities are due to maternal seizures or medications, there is still debate. It is generally believed that the risk of teratogenicity caused by poorly controlled seizures may be greater than the teratogenicity of medication. Clinically, patients who can control the onset with phenytoin should continue to use it during pregnancy and maintain an effective blood concentration. Due to changes in the absorption and metabolism of phenytoin sodium during pregnancy, the blood concentration should be monitored frequently. In case of increased seizures, the dosage should be increased and readjusted after delivery.

(4) Newborn babies born to pregnant women taking phenytoin have an increased risk of life-threatening bleeding (usually within 24 hours of birth). Phenytoin can also reduce the mother's vitamin K and also increase the risk of bleeding during childbirth. Preventively giving the mother a water-soluble vitamin K one month before and during childbirth, and giving the newborn a intravenous vitamin K immediately after childbirth can reduce bleeding. Dangerous.

(5) Sodium phenytoin can be secreted into breast milk through the breast. For safety reasons, it is generally advisable not to breastfeed with phenytoin.

(6) The incidence of chronic hypoproteinemia in the elderly is often high, and there are many combined medications in the treatment, and the interactions between the drugs are complicated. Therefore, the elderly should be cautious when using phenytoin, the dosage should be low, and frequent monitoring Blood drug concentration. The speed of intravenous injection needs to be slowed down, not exceeding 50 mg within 2-3 minutes. Older people are more drowsy, so it is best to take it before bedtime.

(7) Because the volume of distribution and elimination half-life in children vary with age, pediatric patients should often make blood drug concentrations. The apparent distribution volume of premature babies is 1.2L / kg on average, and 0.8L / kg for full-term babies, which remains constant for 96 weeks. The phenytoin protein binding rate of newborns is reduced within three months, and free phenytoin can be increased by 40%, so the total blood concentration is maintained at a low level of 6-14 g / ml, and the phenytoin T1 / 2 of premature infants is significantly prolonged. , Reflects the immature nature of the liver and is not easy to metabolize phenytoin. Infants affected by phenytoin in the womb have a faster metabolic rate and may be induced by liver metabolic enzymes

result. Due to the pharmacokinetics of phenytoin in neonates and infants, it is difficult to evaluate the symptoms of poisoning clinically. Generally, this product is not considered first. Preschool children need to systematically determine the blood concentration to determine the daily dosage and frequency of administration. Some children need 15 mg / kg daily to maintain the therapeutic concentration. Due to the strong and rapid liver metabolism during childhood, the half-life is short. Symptoms of poisoning may occur during the peak period, and when the blood level is low, it is suspected that the blood drug concentration is too low and the attack occurs. Be sure to measure the blood drug concentration multiple times to understand the details of the fluctuation.

(8) The more common complication of phenytoin is gingival hyperplasia. Gingivitis usually occurs within 6 months after the start of treatment. The incidence of children under 15 years is higher than that of adults. The anterior gingival hyperplasia is more severe than the posterior. If the oral hygiene is strengthened and splints are added within 10 days of the start of treatment, the speed and degree of gum growth can be reduced.

(9) Pay attention to check during medication: blood and platelet count, liver function, lymph nodes, skin, calcium, oral cavity, EEG, blood concentration and thyroid function. Blood concentrations must be followed up frequently to prevent toxic reactions. During pregnancy, one test is performed monthly to determine whether an increase in dosage is needed and once a week after delivery to determine whether a reduction is needed.

(10) In order to reduce gastrointestinal reactions, it should be taken immediately after meals or with milk. It should be taken on time. If it is missed, it should be taken immediately 4 hours before the next dose. Do not take two doses at a time.

(11) Diabetes patients should measure the amount of urine sugar. If surgical treatment is needed, their medical history and medication should be explained. Use caution when driving a car, operating a machine, or performing work that requires extreme alertness. Pay attention to oral hygiene and clean your teeth to prevent gum bleeding and swelling.

(12) The individual difference of this product is very large, the dosage needs to be individualized, and some patients can have symptoms of poisoning when using up to 150mg, and many patients also have symptoms of poisoning at 300mg per day. After proper reduction, the treatment can be achieved The symptoms of poisoning also disappeared, so the daily daily dosage of Chinese people is between 250-300mg, and individual patients can increase it in moderation. Westerners' 300mg daily is often not enough. The metabolism of phenytoin in elderly or severely ill patients or patients with impaired liver function tends to be slow, so the possibility of reaching toxic concentrations increases. Patients with reduced albumin or reduced protein binding may have symptoms of poisoning at low blood concentrations, and the dosage should be reduced. If intravenous injection is needed, the injection rate should be slowed down, not exceeding 50 mg every 2-3 minutes. Decrease the dose gradually when you decide to stop the medicine, so as not to have more frequent attacks or even a sustained state.

(13) Patients cannot tolerate or have an allergic reaction and need to discontinue the drug immediately, usually after 9-14 days of observation after starting treatment. If the rash is urticaria-like or blush-like fever, it can be tried again after the rash subsides. If the rash returns, it should be discontinued. If the rash is flaky, purpuric, bullous, or lupus erythematosus, or suspected of having severe polyerythroid erythema, you should not try again. If lymph nodes are enlarged, a differential diagnosis of lymph node enlargement is required.

(14) When symptoms of central nervous system or cerebellar poisoning appear, reduction or withdrawal can improve or disappear. The effects of the central nervous system often occur after long-term application and the blood concentration exceeds 30 g / ml, occasionally at low concentrations. Vitamin D and calcium metabolism disorders, a large amount of vitamin D2 can be given first, 4000 units per day for 4 months, and the daily maintenance amount of 1,000 units, there is no need to preventive administration. This product can increase atrioventricular conduction, so when ventricular arrhythmia is combined with atrial fibrillation or atrial flutter, the ventricular rate can be increased, and the ventricular rate can be increased due to the reduction of atrioventricular node occult conduction.

Phenytoin adverse reactions

1. More common are changes in behavior, awkwardness or unstable gait, confusion, persistent nystagmus, increased seizures, mental changes, weakened muscles, articulation, hand shake or long-term application of the central nervous system or Cerebellar poisoning caused by abnormal excitement, nervousness or irritability, swollen gums, bleeding, hairy;

2. Rarely, cervical or axillary lymphadenopathy (decreased IgA), fever or rash (intolerance or allergy);

3. Rare reactions include dark urine, light stools, decreased appetite, severe stomach pain, yellow eyes or skin (hepatitis or stagnation jaundice), fractures, bone abnormalities or slow growth (vitamin D and calcium Metabolic disorders), sore throat and fever (granulocytosis or resistance), bleeding or bruising (thrombocytopenia);

4. Symptoms of overdose are blurred vision or double vision, clumsiness or instability and faltering, confusion, severe dizziness or drowsiness, hallucinations, nausea, and slurred speech. Drowsiness, itching, dizziness, headache, nausea, vomiting, rash. Muscle tremors, blurred vision, purpura, mental disorders or disorders. Excessive injection can cause hypotension, bradycardia, atrioventricular block, vascular collapse, and respiratory depression. Giant cell anemia is common. In some cases, leukopenia was reduced and aplastic anemia. Long-term use in children affects bone growth (or osteomalacia) and gingival hyperplasia. It can cause central nervous system depression, cerebellar dysfunction, dyskinesia, and peripheral neuropathy.

Gingival hyperplasia is its typical and troublesome adverse reaction. Interstitial pneumonia, interstitial nephritis can occur, and liver damage can occasionally occur. Intravenous high doses can cause cardiotoxic effects. It can produce allergic syndromes with skin, muscle, lung, blood, reticuloendothelial system, liver, kidney, and blood vessel damage and fever. Neuroblastoma can occur with fetal phenytoin syndrome. It can cause pseudolymphoma rather than malignant lymphoma.

[Cardiovascular System]

Oral phenytoin has little effect on the heart when treating epilepsy, and sometimes a significant drop in blood pressure can occur. Intravenous low doses can cause temporary hypotension and even induce arrhythmias. Intravenous high doses can cause severe bradycardia, hypotension, and syncope. One case reported allergic myocarditis. When this medicine is used to treat arrhythmias, occasionally irreversible heart rhythm changes such as ventricular tachycardia can be induced, which can lead to death. This drug should be discontinued before surgical anesthesia to avoid intraventricular or intraventricular conduction disturbance during operation.

[Respiratory system]

Fever, dyspnea, hypoxemia, and bilateral pulmonary infiltration caused by this drug induced acute allergic vasculitis, the pathological process is interstitial pneumonia with diffuse inflammatory exudate invasion and alveolar cavity and interstitial tissue , Cause alveolar wall thickening, inflammation also invades the perivascular stroma and vascular wall. Withdrawal and application of corticosteroids are effective.

[nervous system]

When the concentration of phenytoin in the blood reaches 30 to 40 g / ml, ataxia will occur, and sleepiness and language disorders will occur when the phenytoin concentration rises, and even at normal treatment doses, cerebellar syndrome with ataxia, nystagmus, and articulation Obstacles and tremors. Some reports of phenytoin may cause true cerebellar atrophy, especially in patients with severe encephalopathy and mental abnormalities, confirmed by air-brain angiography and CT examination, and histology confirmed cerebellar degeneration. Should be considered due to recurrent long-term hypoxia caused by frequent seizures. However, there are reports that it is obviously related to the length of the disease and the total amount of medication, but not to the number of attacks. Phenytoin can cause movement disorders, with dancing hand, foot and asthma common; occasionally dystonia. Aggravated myasthenia gravis, Parkinson's syndrome, and exacerbation of tardive dyskinesia have been reported. Excessive exercise is only seen in serum phenytoin concentrations that are too high, especially in patients with organic damage to the brain. Occasionally, peripheral neuropathy, but milder, if the reflex disappears without muscle wasting and weakness, feeling unchanged or slightly changed. Application of folic acid is effective.

[Digestive system]

Gingival hyperplasia occurred in 40 to 80% of patients treated with phenytoin, and it was related to dose and serum concentration. Such as thoroughly removing tartar from the gums and brushing your teeth, paying attention to oral hygiene can reduce it, and the application of folic acid is effective. One application of phenytoin can cause diarrhea. Phenytoin can cause toxic hepatitis.

[Urinary system]

Due to phenytoin allergic reactions, occasional interstitial nephritis with reversible renal failure is usually accompanied by rash, myositis, fever, lymphadenopathy, eosinophilia, and allergic hepatitis. Withdrawal and application of corticosteroids can recover. Nephrotic syndrome has been reported with mephenytoin.

[Hematopoiesis system]

Phenytoin can cause megaloblastic anemia, whole-cell anemia, and disseminated lupus erythematosus, but it is very rare; and mephenytoin has seen aplastic anemia. Other reports of granulocytopenia, hemolytic anemia with renal failure, and simple erythrocyte agenesis. It has been reported that the long-term application of phenytoin to prevent seizures can produce its own antibodies and inhibitors of neutralizing factor , resulting in spontaneous hemophilia acquired the day after tomorrow.

[Endocrinology, metabolism]

Phenytoin significantly reduces blood thiamine. It affects the liver's lipid metabolism and can induce or exacerbate triglycerides and cholesterol elevation. Phenytoin can persistently increase high-density lipoprotein cholesterol in the blood, and nearly half of patients exceed the normal range, which may help prevent the occurrence of coronary heart disease. Phenytoin inhibits insulin secretion and causes an increase in blood glucose. Patients who used phenytoin in a large amount compared with healthy controls, found that serum alkaline phosphatase, alanine aminotransferase and plasma prothrombin time were significantly increased, and serum albumin, calcium and bilirubin were decreased. Serum copper in patients receiving phenytoin increased twice, regardless of dose.

[Special senses]

When the increase of serum phenytoin concentration has a significant effect on consciousness (35-55 g / ml), all extraocular muscles can be paralyzed. After the patient recovers, although the eye movement recovers, the eye-brain reflex and eye- vestibular reflex are still suppressed Phenytoin appears to have a direct inhibitory effect on the vestibular-eye motor system, which is stronger than inhibiting other parts of the nervous system. A serum concentration slightly higher than the therapeutic concentration is sufficient to induce nystagmus. Iris tremor can occur when phenytoin is poisoned.

[skin]

Various rashes can occur, mostly maculopapular erythema, and those with polymorphic erythema also occur. There have been reports of post-auricular fold hyperplasia and epidermal necrolysis. Intravenous injection has a skin and soft tissue reaction at the injection site, which manifests as local bruising and develops erythema and edema, and even blisters and bullae occur. Diffuse fasciitis with eosinophilia and hypergammaglobulinemia has been reported. The skin and subcutaneous tissues in the arms and lower legs are thickened, and the changes in the face, hands, and feet are mild.

[Reticulated endothelial system]

Phenytoin acts on the reticuloendothelial system to make lymph nodes, hepatosplenomegaly (generally reversible), and induces pseudolymphoma, which is an allergic reaction. There have been reports of irreversible malignant lymphoma with phenytoin.

[immune response]

Many reports have suggested that IgA levels in the blood of patients receiving phenytoin are reduced. Under the influence of antiepileptic drugs, cellular immune dysfunction may be related to the increased risk of lymphoma mentioned above. Renal transplantation patients also use phenytoin to treat recurrent epilepsy. Phenytoin can increase the metabolism of immunosuppressive corticosteroids and affect the survival of transplanted kidneys. Phenytoin allergy syndrome, ranging from rash with fever to fulminant lethal exfoliative dermatitis, vasculitis, and diffuse intravascular coagulation. The most common are fever, eosinophilia, lymphadenopathy, hepatosplenomegaly, atypical lymphocytic blood disease, serum disease, hepatitis, and renal failure, which appear in combination with polymyositis.

[excess]

Oral overdose can cause disturbance of consciousness, hypotension, respiratory depression, restlessness, pouting, panic twitching, cold and cold skin, hyperreflexia, irritability, and positive dysfunction.

Contraindications to phenytoin

1. The following conditions should be disabled; patients with a history of allergies to hydantoin and asthma syndrome, II-III degree atrioventricular block, sinoatrial block, sinus bradycardia and other cardiac impairment.

2. The following situations should be used with caution:

Alcohol, the blood concentration of this product can be reduced;

Anemia, increased risk of serious infections;

Cardiovascular diseases, especially the elderly, can cause ventricular fibrillation or reduce stroke volume when injecting medicine;

Diabetes and blood sugar may increase;

hepatic impairment, metabolic changes of this product;

Impaired renal function can affect excretion of this product;

Abnormal thyroid function may reduce serum T4 concentration due to accelerated catabolism. Pediatric long-term use affects bone growth (or osteomalacia) and gingival hyperplasia. May be teratogenic, pregnant women are prohibited. With phenytoin at the end of pregnancy, the infant's coagulation factor is suppressed enough to cause bleeding, in which case vitamin K should be given.

Phenytoin interaction

1. Long-term application of acetaminophen in patients with phenytoin can increase the risk of liver poisoning and reduce the efficacy.

2. When combined with corticosteroids, glucocorticoids and mineralocorticoids, oral contraceptives containing estrogen, adrenocorticotropic hormone, cyclosporin, digitalis, estrogen, levodopa or quinidine The efficacy of these drugs can be reduced because phenytoin induces liver metabolic enzymes.

3. Long-term drinking can reduce the concentration and efficacy of phenytoin sodium, but taking large amounts of alcohol while taking phenytoin can increase the blood concentration; and anticoagulants such as coumarins or chloramphenicol, isoniazid, butazone, sulfonamide Combined use, because they can reduce the metabolism of phenytoin sodium, it may increase the effect and / or toxicity of phenytoin sodium; when combined with coumarin anticoagulants, the anticoagulant effect can be increased at the beginning, but it is reduced when it is continuously applied .

4. When combined with antacids containing magnesium, aluminum or calcium carbonate, the bioavailability of phenytoin sodium may be reduced. The antacids should be taken separately from phenytoin or phenytoin sodium 2 to 3 hours apart.

5. When used with oral hypoglycemic agents or with insulin, you may need to pay attention to and adjust the dosage of the latter two, because phenytoin can increase blood sugar.

6. In patients with long-term use of dopamine, intravenous hypophenytoin may cause sudden hypotension and slow heart rate, and it is believed to be related to the latter's dosage and absorption rate. In principle, patients using dopamine need anticonvulsants, The use of phenytoin should not be considered.

7. Intravenous phenytoin combined with lidocaine or propranolol (propranolol) may strengthen the heart's inhibitory effect.

8. Although phenytoin consumes folic acid in the body, adding folic acid instead can reduce the concentration of phenytoin and weaken the control of the attack.

9. The effect of phenobarbital or primidone on phenytoin varies greatly, and the blood concentration should be frequently tested; when combined with valproic acid or sodium valproate, it has a competitive effect on protein binding rate and should be monitored frequently Blood concentration, and adjust the amount of phenytoin sodium according to clinical conditions.

10. The combination of phenytoin sodium and carbamazepine can reduce the blood concentration of carbamazepine by inducing enzymes in liver metabolism; it is estimated that 1 mg / kg of phenytoin sodium can reduce the blood concentration of carbamazepine by 0.5 g / ml. If a large number of antipsychotic drugs or tricyclic antidepressants are used in combination, seizures may be induced, and central nervous system inhibition may be more obvious. The amount of phenytoin sodium needs to be adjusted. Isoniazid, abstinence sulfur, sulfamethoxazole, chloramphenicol, miconazole, bute pine and dicoumarin increase serum phenytoin concentration and increase its toxic effect. Phenytoin can enhance the effects of antihypertensive drugs, diuretics, digitalis, quinidine, procainamide, and propranolol. Phenytoin reduces the blood concentration of dexamethasone, and dexamethasone also increases the concentration of phenytoin. Phenytoin reduces the effects of oral contraceptives and has been reported to increase the chance of conception by a factor of 25. Phenytoin interacts with proteins and calcium in nasal feeds, resulting in a decrease in the bioavailability of phenytoin. If you do not know this, increase the dose when the serum concentration decreases, and poisoning will occur if nasal feeding is stopped.

Phenytoin drug preparation

Phenytoin sodium tablets

1.50mg 2.100mg

Phenytoin sodium for injection

1.100mg2.250mg

1. Anti-epilepsy: 50-100mg a day orally, 2-3 times a day, after meals.

Dosage: 0.3 at a time, 0.6g a day. Children weighing less than 30kg should be administered at 5-10mg / kg daily and divided into 2-3 times. For continuous status of epilepsy, 100-250mg intramuscularly, 100-150mg after 30 minutes.

2. Treat trigeminal neuralgia: 100-200mg each time, 2-3 times a day.

3. Treatment of arrhythmia: take 100-200mg each time, 2-3 times a day, or 125-250mg, add 5% glucose injection 20-40ml slowly and intravenously within 5-15 minutes (not more than 50mg per minute) . Repeatedly inject 100mg every 5-10 minutes if necessary, not exceeding 500mg for 2 hours. Intravenous infusion with the same dose dissolved in 100ml of 5% glucose injection, the daily amount does not exceed 1000mg, intramuscular injection of 200-400mg a day.

4. Treatment of hypertension: take 100mg daily, 3 times a day.