Side Effects of phenytoin: A Synthesis of Findings from 13 Studies

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Original Abstract of the Article

Major Research Findings

Phenytoin is a common antiepileptic drug used to treat seizures and other neurological conditions. However, phenytoin can cause a variety of side effects. This article presents the latest research findings on the side effects of phenytoin.

Phenytoin can cause serious side effects such as drug-induced gingival overgrowth ( 5 ), Stevens-Johnson syndrome ( 2 ), and toxic epidermal necrolysis ( 2 ).

Phenytoin can also cause hypocalcemia in patients with vitamin D deficiency, which can worsen seizure control ( 10 ).

Phenytoin's efficacy is reduced by plasma protein binding, which sequesters therapeutically active drug molecules in the bloodstream. A focused ultrasound (FUS) technique has been developed to enhance the efficacy of phenytoin by transiently disrupting its binding to albumin ( 7 ).

Reasons for Side Effects

The exact mechanisms of phenytoin's side effects are not fully understood, but they are believed to involve reduced intracellular folate levels, dysregulation of collagenase activity, as well as integrins and membrane receptors, resulting in reduced degradation or excessive synthesis of connective tissue components ( 5 ).

Common Side Effects

Gingival Overgrowth

Phenytoin is well-known to cause gingival overgrowth ( 5 ).

Hypocalcemia

Phenytoin can cause hypocalcemia, especially in patients with vitamin D deficiency, which can worsen seizure control ( 10 ).

Skin Reactions

Phenytoin can cause serious skin reactions such as Stevens-Johnson syndrome ( 2 ) and toxic epidermal necrolysis ( 2 ).

Neurological Disorders

Phenytoin can cause neurological disorders, such as cerebellar atrophy ( 1 ).

Liver Injury

Phenytoin can cause liver injury ( 12 ).

Countermeasures for Side Effects

Gingival Overgrowth

Gingival overgrowth can be prevented or reduced by improving oral hygiene, using a toothbrush, and having regular checkups with a dentist.

Hypocalcemia

Hypocalcemia can be prevented or reduced by supplementing with calcium and vitamin D.

Skin Reactions

Early detection and treatment of skin reactions are crucial. If skin reactions occur, seek immediate medical attention.

Neurological Disorders

Neurological disorders may improve if phenytoin administration is stopped.

Liver Injury

Liver injury can be detected early through regular liver function tests. If abnormalities are found in liver function tests, phenytoin administration may need to be stopped.

Comparison Between Studies

Commonalities in Studies

Multiple studies have shown that phenytoin can cause various side effects.

Differences in Studies

The frequency and severity of side effects reported in each study vary.

Precautions for Real-Life Applications

Phenytoin is an effective antiepileptic drug, but it can cause various side effects. It is important to understand the risks and benefits of phenytoin and to take it as directed by your doctor if you are taking phenytoin.

Current Research Limitations

Research on phenytoin's side effects is still insufficient. Further research is needed.

Future Research Directions

It is necessary to elucidate the mechanisms of phenytoin's side effects and develop new treatment and prevention methods.

Conclusion

Phenytoin is an effective antiepileptic drug, but it can cause a variety of side effects. It is important to understand the risks and benefits of phenytoin and to take it as directed by your doctor if you are taking phenytoin. Further research is expected to deepen our understanding of phenytoin's side effects and develop safer treatment methods.

Literature analysis of 13 papers

Positive Content

Neutral Content

Negative Content

Article Type

Randomized Controlled Trial0

Meta-Analysis0

Systematic Review0

Review5

Journal Article10

Phenytoin-induced cerebellar atrophy: A case for reversibility of neurological decline.

Author: MogereEdwin, CheruiyotDavis, NassiumaManakhe

Improved cerebellar function

Cerebellar degeneration

This case study highlights the potential for cerebellar degeneration in patients on long-term phenytoin treatment. The patient experienced neurological impairment and severe cerebellar atrophy which improved after cessation of phenytoin.

Language : English

Phenytoin-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Overlap in Focus: A Case Report.

Author: PuriPiyush, AslamZaid M, KomalFnu, PrachiFnu, SardanaPrincy, ChitkaraAkshit

None mentioned

Stevens-Johnson syndrome

Toxic epidermal necrolysis

This case report describes a 10-year-old boy who developed Stevens-Johnson syndrome and toxic epidermal necrolysis overlap after receiving phenytoin for seizures. The case emphasizes the importance of early recognition and aggressive management of this severe hypersensitivity reaction.

Language : English

Therapeutic Drug Monitoring (TDM) Implementation in Public Hospitals in Greece in 2003 and 2021: A Comparative Analysis of TDM Evolution over the Years.

Author: VoulgaridouGavriela, ParaskevaTheodora, RagiaGeorgia, AtzemianNatalia, PortokallidouKonstantina, KoliosGeorge, ArvanitidisKonstantinos, ManolopoulosVangelis G

Personalized medicine

Side effect prevention

Treatment efficacy

TDM implementation decline

This study assessed the current status of therapeutic drug monitoring (TDM) in Greek public hospitals. The findings show a significant decrease in TDM implementation, highlighting the need for efforts to reverse this trend.

Language : English

Antiseizure Medication-Induced Alopecia: A Literature Review.

Author: Pitton RissardoJamir, Fornari CapraraAna Leticia, CasaresMaritsa, SkinnerHolly J, HamidUmair

Alopecia

This literature review examines alopecia as a side effect of antiseizure medications (ASMs). Valproate, lamotrigine, and carbamazepine are the most frequently reported ASMs associated with alopecia. Alopecia is typically diffuse, non-scarring, and often reversible after ASM dose adjustments.

Language : English

Drug-Induced Gingival Overgrowth-Molecular Aspects of Drug Actions.

Author: DroździkAgnieszka, DroździkMarek

Gingival overgrowth

Drug-induced gingival overgrowth (DIGO) is a side effect of certain medications, most commonly phenytoin, nifedipine, and cyclosporin A. The exact cause of DIGO is unclear, but it likely involves a combination of factors, including calcium channel antagonism and reduced intracellular folic acid levels. These factors lead to altered cellular function, ultimately resulting in increased collagen and glycosaminoglycans accumulation in the gums.

Language : English

Management of noncytotoxic extravasation injuries: A focused update on medications, treatment strategies, and peripheral administration of vasopressors and hypertonic saline.

Author: StefanosSylvia S, KiserTyree H, MacLarenRobert, MuellerScott W, ReynoldsPaul M

Hypertonic sodium

Peripheral vasopressor

Extravasation injuries

Tissue damage

This review explores extravasation, the leakage of intravenous solutions into surrounding tissues. It discusses the various factors influencing extravasation, including drug properties, infusion techniques, and patient-related risk factors. The review also examines the physiochemical causes of tissue injury, including vasoconstriction, pH-mediated, osmolar-mediated, and cytotoxic mechanisms. It further highlights pharmacological antidotes and management strategies, emphasizing a multidisciplinary approach for early detection, treatment, and surgical referral when necessary.

Language : English

Transcranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model.

Author: KimEvgenii, KimHyun-Chul, Van ReetJared, BöhlkeMark, YooSeung-Schik, LeeWonhye

Epilepsy treatment

Drug side effects

This study presents a low-intensity focused ultrasound (FUS) technique that locally enhances the efficacy of PHT by transiently disrupting its binding to albumin in rats with chronic mesial temporal lobe epilepsy (mTLE).

Language : English

Ketamine as advanced second-line treatment in benzodiazepine-refractory convulsive status epilepticus in children.

Author: BurattiSilvia, GiacheriEmanuele, PalmieriAntonella, TibaldiJessica, BriscaGiacomo, RivaAntonella, StrianoPasquale, MancardiMaria Margherita, NobiliLino, MoscatelliAndrea

Refractory SE Treatment

Ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, shows potential as a second-line treatment for status epilepticus (SE) refractory to benzodiazepines, offering antiepileptic, neuroprotective, and synergistic effects with other antiseizure medications.

Language : English

Efficacy of 48 hours dose of phenytoin in prevention of early post-traumatic seizure.

Author: OyemoladeToyin Ayofe, AdeoluAugustine A, BadejoOluwakemi A, BalogunJames A, ShokunbiMatthew T, MalomoAdefolarin O, AdeleyeAmos O

Seizure prevention

Side effects

This study investigates the efficacy of a short-course (48-hour dose) of phenytoin in preventing early post-traumatic seizures. Phenytoin has been shown to reduce the incidence of early post-traumatic seizures in some studies, but concerns exist regarding its side effects. The study aims to evaluate the effectiveness of a short-term dose of phenytoin in minimizing these risks.

Language : English

10.

Loss of Seizure Control in a Patient With Vitamin D Deficiency and Phenytoin-Induced Hypocalcemia.

Author: BrancoTiago, CardosoAna, BaltazarAna, GonçalvesCatarina, SantosVera C

Seizure control

Hypocalcemia

This case report describes a 69-year-old woman with long-term phenytoin treatment who developed persistent hypocalcemia and seizures despite treatment with multiple antiepileptic drugs. The hypocalcemia was refractory to supplementation until phenytoin was discontinued, after which seizure control was achieved. This case highlights the importance of regular monitoring and supplementation for patients on long-term phenytoin treatment.

Language : English

11.

Features of the choice and the use of antiepileptic drugs as analgesics in elderly.

Author: UshkalovaE A, ZyryanovS K, ButranovaO I

Chronic pain management

Side effects

This review explores the use of antiepileptic drugs for managing chronic pain in the elderly, considering both "old" and "new" antiepileptics. It provides insights into pharmacokinetic features, side effects, and analgesic efficacy in this population.

Language : English

12.

Clinical and Liver Biochemistry Phenotypes, and Outcome in 133 Patients with Anti-seizure Drug-Induced Liver Injury.

Author: DevarbhaviHarshad, SridharAarthi, KurienSunu Sara, GowdaVinod, KothariKsheetij, PatilMallikarjun, SinghRajvir

Anti-seizure drug hepatotoxicity

DILI

This study investigated the clinical and demographic characteristics, the liver injury pattern, the outcome, and the agents responsible for hepatotoxicity in a large cohort of DILI registry patients.

Language : English

13.

Efficacy of phenytoin for 7 days versus 21 days as prophylactic anticonvulsant in traumatic brain injury patients - A comparative study.

Author: KumarSantosh, BhartiAlok Kumar, PrasadRavi Shankar, KumariSarita, SinghAnup, YadavGhanshyam

PTS treatment

Post traumatic seizures (PTS) are common after traumatic brain injury, especially in severe cases. Prophylactic treatment with phenytoin is effective, but there are no uniform international guidelines for the duration of anticonvulsant prophylaxis.

Language : English

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