Aplastic Anemia Secondary to Anticonvulsants

Robins, M. Moreno

doi:10.1001/archpedi.1962.02080030614006

Cited by 10 publications

(5 citation statements)

References 60 publications

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“…Therefore, it is important to educate patient regarding the offending agent and to avoid further exposure. [10] Clinicians and clinical pharmacist should have adequate knowledge regarding such reactions and they must give careful attention to such patients. The patient developed aplastic anemia after 2 years use of phenytoin.…”

Section: Resultsmentioning

confidence: 99%

Phenytoin-induced aplastic anemia in generalized tonic clonic seizures patient: A case report

Bindu¹,

Naik²,

Krishnaveni³

et al. 2020

IJMS

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Aplastic anemia is a hematopoietic stem cell disorder characterized by pancytopenia of the peripheral blood and hypocellular bone marrow. Phenytoin is the most commonly and most widely used anticonvulsant, which is used for the prevention and treatment of generalized seizures, partial seizures, and status epileptics. The main aim of the study is to enlighten the drug-related problem and address such problems to prevent the occurrence of adverse event and optimizing drug therapy. Here, we present a case of a 35-year-old female patient who was admitted with complaints of fever, breathlessness, and lower limb swelling. She is a known case of hypertension and generalized tonic clonic seizures for which was taking tablet amlodipine and tablet phenytoin from 5 and 2 years, respectively, after which the patient developed aplastic anemia.

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Section: Resultsmentioning

confidence: 99%

Phenytoin-induced aplastic anemia in generalized tonic clonic seizures patient: A case report

Bindu¹,

Naik²,

Krishnaveni³

et al. 2020

IJMS

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“…The choice of phenytoin as the primary drug has certain advantages. Mephenytoin is limited by frequent toxic reactions (16), and its use is rarely warranted. Serious side effects are rare and almost always reversible.…”

Section: B Medication Choices: Partial Seizuresmentioning

confidence: 99%

“…One additional hydantoin is worthy of mention even though it is rarely utilized. Mephenytoin is limited by frequent toxic reactions (16), and its use is rarely warranted. Finally, phenacemide is a ring-opened analog of phenytoin, but also has frequent idiosyncratic toxicity, including organ toxicity and personality changes (17).…”

Section: B Medication Choices: Partial Seizuresmentioning

confidence: 99%

Current medical therapy of epilepsy

Porter

1992

Acta Neurologica Scandinavica

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“…With regard to certain side effects, such as gum hypertrophy, hypertrichosis, and dose-related neurological toxicity, MHT compares favorably with phenytoin (Troupin et al, 1976). However, idiosyncratic side effects, such as skin rash, drug fever, generalized adenopathy, and, particularly, aplastic anemia, are more likely to occur with MHT (England and McEachern, 1949;Abbott and Schwab, 1954;Robins, 1962). In vivo demethylation of MHT produces 5-phenyl-5-ethylhydantoin (PEH; normephenytoin) (Butler, 1952), which is also an anticonvulsant and has the same chemical structure as nirvanol, a drug no longer in use because of its marked side effects, including bone marrow aplasia (Jones and Jacobs, 1932;Schick et a]., 1933).…”

mentioning

confidence: 99%

Pharmacokinetics of R‐Enantiomeric Normephenytoin During Chronic Administration in Epileptic Patients

et al. 1986

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Stereoselective metabolism has been demonstrated for mephenytoin (MHT), R-MHT being demethylated to the pharmacologically active metabolite 5-phenyl-5-ethylhydantoin (PEH; nirvanol), and S-MHT undergoing aromatic hydroxylation to 4-OH-MHT, with formation of an intermediate arene oxide metabolite. PEH is responsible for the therapeutic effect, whereas 4-OH-MHT is rapidly eliminated by the kidneys. The arene oxide metabolite may have implications in MHT toxicity. The metabolism of PEH is also stereospecific. In the present study, the R-enantiomer of PEH (R-PEH; R-normephenytoin) was administered chronically during 8 weeks to four epileptic patients, as a single dose every 3 days. The half-lives of R-PEH ranged from 77.7 to 175.8 h, and correlated closely with the creatinine clearance. Mean urinary recovery of R-PEH was 86.6% of the dose at steady state, with 4-OH-PEH accounting for only 5%. This indicates that, unlike Nirvanol (a racemic mixture of R- and S-PEH), R-PEH is only minimally metabolized, even after several weeks of treatment and despite potential enzymatic autoinduction and heteroinduction by other antiepileptic drugs. Complete blood counts and liver function tests revealed no alteration, and no other adverse effects were noted. If arene oxide intermediate metabolites are indeed involved in the toxicity of MHT and nirvanol, R-PEH may represent a safer alternative.

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Aplastic Anemia Secondary to Anticonvulsants

Cited by 10 publications

References 60 publications

Phenytoin-induced aplastic anemia in generalized tonic clonic seizures patient: A case report

Phenytoin-induced aplastic anemia in generalized tonic clonic seizures patient: A case report

Current medical therapy of epilepsy

Pharmacokinetics of R‐Enantiomeric Normephenytoin During Chronic Administration in Epileptic Patients

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