Children phenytoin

Burks, A.W. et al., Immune function in patients treated with phenytoin, J. Child Neurol., 4, 25, 1989. 

A child weighing 28 lb is to receive 4 mg of phenytoin per kilogram of body weight daily as an anticonvulsant. How many milliliters of pediatric phenytoin suspension containing 30 mg per 5 mL should the child receive ... 

An 8-year-old child with grand mal seizures experiences nystagmus while on 200 mg/day of long-term phenytoin treatment, given in three divided doses. A steady-state phenytoin concentration of 5.0 mg/L is measured (therapeutic range, 8-20 mg/L). Beside normal laboratory results, it was noted that the child had profound hypoalbuminemia. Free (unbound) phenytoin concentration was 2.4 mg/L (therapeutic range 0.2-2 mg/L). 

Wheless JW. Pediatric use of intravenous and intramuscular phenytoin lessons learned. J Child Neurol 1998 13(Suppl 1) S11-S14 discussion S30-S32. 

Loughnan PM, Greenwald A, Purton WW, et al. 1977) Pharmacokinetic observations of phenytoin disposition in the newborn and young infant. Arch Dis Child 52 302-309. 

In a 5-year-old child who died following the ingestion of flurazepam and phenobarbitone, the following postmortem tissue concentrations were reported for flurazepam, A -desalkylflurazepam and A -(2-hydroxy-ethyl)flurazepam, respectively blood 3.2, 1.8 and 2.5pg/ml brain 0.8, 0.7 and 0.7 pg/g, kidney 0.9, 0.6 and 1.1 pg/g, liver 2.7, 3.1 and 3.5 pg/g. Phenobarbitone concentrations were consistent with a therapeutic dose and low concentrations of phenytoin were also detected (S. D. Ferrara et al., J.forens. Sci., 1979, 24, 61-69). 

When a child has febrile convulsions the decision to embark on continuous prophylaxis is serious for the child, and depends on an assessment of risk factors, e.g. age, nature and duration of the fits. Most children who have febrile convulsions do not develop epilepsy. Prolonged drug therapy, e.g. with phenytoin or phenobarbitone, has been shown to interfere with cognitive development, the effect persisting for months after the drug is withdrawn. Parents may be supplied with a specially formulated solution of diazepam for rectal administration (absorption from a suppository is too slow) for easy and early administration, and advised on managing fever, e.g. use paracetamol at the first hint of fever, and tepid sponging. 

Raised blood pressure and proteinuria (preeclampsia) complicates 2-8% of pregnancies and may proceed to fitting (eclampsia), a major cause of mortality in mother and child. Magnesium sulphate halves the risk of progress to eclampsia (tj/pically 4 g i.v. over 5-10 min followed by 1 g/hour by i.v. infusion for 24 hours after the last seizure). Additionally, if a woman has one fit (treat with diazepam), then the magnesium regimen is superior to diazepam or phenytoin in preventing further fits. ... 

Yoshikawa H, Abe T, Oda Y. Purple glove syndrome caused by oral administration of phenytoin. J Child Neurol 2000 15(11) 762. 

WhelessJW. Pediatric Use of Intravenous and Intramuscular Phenytoin Lessons Learned./ Child Neurol 1998 13 Sll—S14, discussion S30—S32. 

Oil of sassafras has been reported to interfere with serum phenytoin concentration determination. A 4-mo-old boy was admitted to the hospital for failure to thrive and possible child abuse after an outpatient visit revealed that he was below the third percentile for height and weight, and had scattered bruises, including one above the left eye. The child s mother had a seizure disorder and was taking phenytoin and phenobarbital. It was suspected that she may have... 

Phenytoin toxicity occurred in a child following halothane anaesthesia. A near fatai hepatic reaction occurred in a woman given rifampicin (rifampin) after haiothane anaesthesia, and hepatitis occurred in a patient taking phenobarbitai who was given halothane anaesthesia. See aiso Anaesthetics, generai H- Isoniazid , p.lOO and Anaesthetics, general Methoxyflurane H- Antibacterials or Barbiturates , p.l07. 

A 3-year-old child taking both phenobarbital and phenytoin required quinidine 300 mg every 4 hours to achieve therapeutic serum quinidine levels, and had an estimated quinidine half-life of only 1.4 hours. Difficulty in achieving adequate serum quinidine levels was also reported in a woman taking phenytoin and primidone. Her quinidine half-life was... 

Another study eonfirmed that this interaction occurred in 20 neonates, but no statistically significant effect was found in 40 infants. Decreased chloramphenicol levels have been described in a single case report of a child who was also being treated with phenytoin and phenobarbital. The serum chloramphenicol levels were 35.1 micrograms/mL prior to the antiepileptics, 19.1 micrograms/mL after 2 days of phenytoin and 13.2 micrograms/mL a month after the addition of phenobarbital. For more information on the interaetion of ehloramphenieol with phenytoin see Phenytoin + Chloramphenieol , p.555. 

Yokochi K, Yokochi A, Giiba K, Ishizaki T. Flienytoin-allopmnol intemction Michaelis-Menten kinetic parametem of phenytoin with and without allopurinol in a child with Lesch-Nyhan syndr ne. TherDrugMornt (1982) 4,353-7. 

A child given a 6-week eourse of intravenous chloramphenicol 100 mg/kg daily in four divided doses had a reduction in chloramphenicol peak and trough serum levels of 46% and 74%, respectively, within 2 days of starting phenytoin 4 mg/kg daily. Levels were further reduced by 63% and 87%, respectively, by the addition of phenobarbital 4 mg/kg daily. Consider also Chloramphenieol + Phenobarbital , (p.300). In contrast, 6 children (aged 1 month to 12 years) developed raised, toxic chloramphenicol levels while reeeiving phenytoin. ... 

A child receiving phenytoin 29 mg/kg daily and an adult receiving phenytoin 1 g daily were unable to achieve therapeutic phenytoin serum levels while taking diazoxide. When the diazoxide was withdrawn, satisfactory serum phenytoin levels were achieved with dosages of only 6.6 mg/kg and 400 mg daily, in the child and the adult, respectively. When diazoxide was restarted experimentally in the adult, the serum phenytoin levels became undetectable after 4 days, and seizures occurred. Two other reports describe this interaction. " In addition it appears that the effects of the diazoxide can also be reduced. ... 

A further case of phenytoin toxicity occurred in another child given methylphenidate. Only one other case has been reported, but this patient was later rechallenged with the two drugs and phenytoin toxicity was not seen. ... 

A child who was stable taking phenytoin and sultiame developed phenytoin toxicity within 48 hours of starting co-trimoxazole. Toxicity resolved when the antibacterial was changed to amoxicillin. A clinical study found that co-trimoxazole and trimethoprim can increase the phenytoin half-life by 39% and 51%, respectively, and decrease the mean metabolic clearance by 27% and 30%, respectively. Sulfamethoxazole alone had only a small effect on the half-life and did not affect the clearance of phenytoin. A case report describes fatal acute hepatic failure in a 60-year-old woman 10 days after starting co-trimoxazole and 14 days after starting phenytoin. This patient was also given cimetidine, which may raise phenytoin levels (see Phenytoin + H2-receptor antagonists , p.559). 

A 5-year-old child with medulloblastoma received a course of topotecan, firstly with phenytoin and then without. Phenytoin increased the total topotecan clearance by 47%. This suggests that an increased topotecan dosage may possibly be needed in the presence of phenytoin in other patients. For a similar effect of antiepileptics on related topoisomerase inhibitors, see Trinotecan + Antiepileptics , p.638 and 9-Aminocamptothecin + Antiepileptics , p.610. 

Mondal R, Sarkar S, Sabui T, Pan PP. Phenytoin induced life threatening macrogjossia in a child. J Neurosci Rural Pract January 2013 4(l) 75-7. 

Pendergrass and Hanson (31 -) recently reported the case of a child with the foetal hydantoin syndrome and neuroblastoma. The 24-year-old mother had been taking phenytoin and phenobarbitone since the age of 14. The pregnancy was complicated by 2 seizures and was terminated by caesarian section at 43 weeks. The child displayed many of the features of the foetal hydantoin syndrome, and at 3 years of age presented with a large abdominal tumour from which she died. Necropsy demonstrated metastatic neuroblastoma. The authors point out that this association may be fortuitous but mention that it has recently been suggested that epoxides may be intermediate products in the metabolism of epanutin and these substances have been reported to be oncogenic. 

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