Phenytoin Therapy Research Articles

Macrolide Antibiotic-Induced Acute Generalized Exanthematous Pustulosis in an Epileptic Patient on Phenytoin Therapy

Macrolide Antibiotic-Induced Acute Generalized Exanthematous Pustulosis in an Epileptic Patient on Phenytoin Therapy

Oral Complications Due to Medication in Stevens-Johnson Syndrome Patient with Systemic Involvement

Background: Stevens-Johnson Syndrome (SJS) is a drug-induced hypersensitivity reaction involving mucocutaneous with various trigger factors including drugs and herpes simplex virus. Objective: This case report aimed to discuss oral complications due to medication in SJS patients with systemic disease involvement. Case: A 51-year-old man was referred to the Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, at Hasan Sadikin Hospital from the dermatology and venereology department complaining of pain in the oral cavity, especially when eating and drinking two months before, with a history of phenytoin, salbutamol and theophylline therapy. Extraoral examination showed erosive lesions and tended to bleed serosanguinolenta crusts on the lips. Intraoral there were erosive lesions and white plaque on the tongue, buccal mucosa, labial mucosa, and palate, as well as dental caries and calculus. Blood examination showed low hemoglobin, hematocrit, erythrocytes, lymphocytes, monocytes, SGOT, and sodium levels, while HbA1c, random, fasting, and 2 HPP glucose levels were high. Reactive Anti-HSV-1 IgG and rheumatoid factor. KOH examination showed positive spores, hyphae, pseudohypha, and budding cells. The diagnosis was SJS-associated oral lesions with HSV-1 virus infection, oral candidiasis accompanied with diabetes mellitus. For diabetes mellitus treatment, he was referred to the internal medicine department. Case Management: The therapy was 0.9% NaCl for lip compress, acyclovir tablet, nystatin oral suspension, chlorhexidine digluconate 0,12% mouthwash, folic acid, and vitamin B12. Oral lesions were improved significantly after diabetes mellitus was treated. Conclusion: The SJS patient was susceptible to complications in the oral cavity, especially fungal and viral infections due to the received medication.

'Double whammy': An Unusual Co-occurrence of Idiosyncratic phenytoin-induced agranulocytosis and acute liver failure in a child.

Idiosyncratic adverse events to phenytoin therapy, such as agranulocytosis and acute liver failure, though rare, may be life-threatening. Simultaneous occurrence of both adverse events is exceedingly rare; only two cases have been reported in the literature to date. We describe such a case in a 15-year-old girl. Prompt haematological and hepatic recovery occurred after discontinuation of the drug. Given the widespread use of phenytoin in seizure disorders, clinicians prescribing this drug should be aware of its potential complications. Early recognition can considerably improve outcomes.

The effect of anticonvulsant drugs on serum lipid profile

BACKGROUND AND OBJECTIVES: Epilepsy is a potentially life-shortening brain disorder, the symptoms of which can be successfully treated in most patients with one or more antiepileptic drug (AED). The literature explains the association of AED therapy and dyslipidemia. The changes in lipid fraction may vary with different AED, age group, and study population. The present study was planned to assess the serum lipid profile of adult epileptic patients receiving phenytoin, carbamazepine or sodium valproate therapy and attending Neurology Outpatient Department of Government Medical College, Kottayam, compared to normal healthy controls. METHODOLOGY: A total of 150 epileptic patients on AED monotherapy attending the outpatient department of neurology were evaluated for serum lipid profile. Demographic data and medical history of consenting participants were collected by the use of a semi-structured questionnaire. Fifty age- and sex-matching healthy controls also underwent similar investigation. RESULTS AND DISCUSSION: Over 12 months, 150 patients were recruited with a mean age of 35.54 ± 10.72 years (male-to-female ratio 1:1.27). When compared to normal control population observed statistically significant high mean total cholesterol, triglyceride level in the group receiving phenytoin therapy for more than 1 year. Only significant hypertriglyceridemia is observed in carbamazepine and sodium valproate treated patients. A significant correlation between the duration of anticonvulsant therapy and lipid profile was established. CONCLUSION: Conventional anticonvulsants induce dyslipidemia and monitoring of lipid profile should be done routinely to decrease the morbidity and preserve the quality of life in these (asymptomatic) patients.

Phenytoin is associated with increased risk of osteoporosis and fragility fractures in adult epileptic patients.

Osteoporotic fractures lead to significant decreases in the quality of life with increases in morbidity, mortality, and disability. Treatment with a variety of anti-epileptic drugs, such as phenytoin, has been understood to cause a decrease in bone mineral density. Cohort A was identified as patients that were 18-55years old that had epilepsy and recurrent seizures that were also prescribed phenytoin. Cohort B was identified as patients that were 18-55years old that had epilepsy and recurrent seizures but were not prescribed phenytoin or other anti-epileptic medications. Cohorts were matched for relevant confounding pathologies and demographic factors. Outcomes were evaluated from 1day to 5years after the indexed event. A total of 35,936 patients with epilepsy that were prescribed phenytoin were matched with 109,335 patients with epilepsy that were not prescribed phenytoin. Patients on phenytoin therapy were at significantly higher risk for osteoporosis without pathological fracture, fracture of metatarsal bone, fracture of shoulder and upper arm, fracture of distal radius, fracture of thoracic vertebra, fracture of cervical vertebra, fracture of lumbar vertebra, fracture of femoral head or neck, pertrochanteric fracture, femoral shaft fracture, and distal tibia fracture (all outcomes p < 0.001). Epileptic patients on phenytoin therapy that were 18-55years old exhibited higher associated risk of osteoporosis and osteoporotic-fragility fractures of various regions. Patients that undergo phenytoin therapy for epilepsy treatment should be educated on the increased risk of bone fractures and have appropriate lifestyle and diet modifications.

A rare case of phenytoin-induced cerebellar atrophy

Epilepsy is a common health problem and affects humans of any age. Phenytoin is indicated in all types of seizure except in absence epilepsy. It has a wide range of pharmacokinetic properties with a narrow therapeutic range thus often leading to toxicity. Long-term neurological side effects of phenytoin include cerebellar atrophy. Therefore, monitoring of plasma levels should be done in patients on long-term phenytoin. Here, we describe a case of cerebellar degeneration in a post-operated brain abscess patient on chronic phenytoin therapy.

Hodgkin lymphoma patient presenting as superior vena cava syndrome in a patient suffering from myotonia congenita: A rare case scenario

A 14-year-old male who was a known case of myotonia congenital (MC) (SCN4A mutation related) on Tab phenytoin therapy presented with progressive shortness of breath, swelling of face, and intermittent fever for 2 months. On investigation, a middle mediastinal mass was diagnosed and histopathological examination along with immunohistochemistry revealed it to be Hodgkin lymphoma (HL). The patient was started on Inj. dexamethasone for superior vena cava syndrome followed by doxorubicin, vincristine, etoposide, and prednisolone chemotherapy and phenytoin dose adjustment. The patient responded well to treatment. This case summarizes the management in patients of HL presenting as superior vena cava syndrome in a background of MC on enzyme inducer therapy.

Phenytoin versus Normal Saline Dressings in the Healing of Chronic Diabetic Foot Ulcers: A Longitudinal Study

Introduction: Chronic wounds, especially the non healing type, are among the foremost common conditions encountered by a surgeon. Currently, steady research is being pursued on the creation of fancy and indulgent topical growth factors for wound healing. One such agent is phenytoin which has a stimulatory effect on connective tissue. Several studies were conducted worldwide to study the effect of phenytoin on chronic ulcers. However, such studies are lacking in our geographical area. Aim: To compare the efficacy of topical phenytoin dressings with conventional saline dressings in the healing of chronic Diabetic Foot Ulcers (DFUs), in terms of the surface area of ulcer, granulation tissue formation as a percentage of the surface area of ulcer, duration of hospital stay, and side effects. Materials and Methods: This was a longitudinal study that included 100 patients with chronic DFUs admitted to a tertiary care hospital, in North Andhra Pradesh for a period of 1 year. The study population was divided into two groups based on the patient’s willingness for undergoing topical phenytoin therapy. Patients willing to undergo the topical phenytoin dressing therapy formed the study group (n=50) and those who were not willing were subjected to traditional saline dressings, which formed the control group (n=50). The variables of the surface area of the ulcer, granulation tissue formation as a percentage of the surface area of the ulcer, duration of hospital stay, and side effects of topical phenytoin dressings were compared using Paired, and Unpaired Student’s t-test, and the p-value of &lt;0.05 was considered significant. Results: The mean age in the study group was 53.94 years and in the control group was 55.92 years. The male:female ratio in the study group was 5:1 and in the control group was 3:1. The mean ulcer surface area in the control group was 37.6 cm2 and in the study group was 40.4 cm2 (p-value=0.012). The mean area of granulation tissue formation in the control group was 36.07 cm2±5.7, and in the study group was 39.63 cm2±2.6 of the total ulcer surface area (p-value=0.001). The granulation tissue formation in the control group was 95.93% of the total ulcer surface area, and in the study group was 98.09% of the total ulcer surface area (p-value=0.001). The mean hospital stay in the control group was 31.3±4.2 days and in the study group was 27.8±2.4 days (p-value=0.001). Conclusion: Phenytoin is better alternative dressing agent with lesser side effects for diabetic foot ulcer care.

Dental management of a child patient with phenytoin-induced gingival overgrowth: report of a case with a brief review of literature

Drug-induced gingival overgrowth is medication-related gingival overgrowth commonly associated with certain systemic medications. Gingival overgrowth is a common adverse effect of phenytoin therapy. The condition is more frequently seen in children as compared to adults, affects both genders equally, and may vary from mild to severe. It may be associated with difficulty in mastication, delayed eruption of teeth, tissue trauma, and secondary inflammation. It can be managed by both surgical and nonsurgical therapies. A case of dental management of phenytoin-induced gingival enlargement in a 7-year-old girl is presented with a brief literature review.

Effectivity of Pyridoxine as Adjuvant Therapy of Phenytoin in Patients with Epilepsy at Soebandi Regional Hospital Jember

Phenytoin is an antiepileptic drug used as monotherapy for partial and generalized tonic-clonic seizures for more than 50 years. Pyridoxine is a water-soluble vitamin widely used for seizure patients unresponsive to standard treatment regimens. This study was conducted to determine the effect of pyridoxine as adjuvant therapy in epilepsy patients receiving phenytoin and to determine the relationship between age, gender, type of epilepsy, and duration of therapy on the incidence of seizures in epilepsy patients at Soebandi Regional Hospital Jember. This research is an observational analytic study with a cross sectional design. The data was taken from the patient's medical record at Soebandi Hospital Jember. The number of samples in each treatment group was 18 samples so the total number of samples in this study was 36 samples. Samples were taken using total sampling technique. Data analysis was performed using Chi-Square test on bivariate analysis and The Logistic test on multivariate analysis. The sample in this study was dominated by male patients (52.8%), aged 19-59 years (52.8%), had epilepsy with generalized seizure type (86.1%), and received therapy for &lt; 3 years (77.8%). The results of bivariate and multivariate analysis showed correlation between the administration of pyridoxine and the incidence of seizures, indicating that phenytoin therapy with pyridoxine adjuvants was more effective than monotherapy phenytoin. Other factors such as gender, age, type of epilepsy, and duration of therapy were not proven to have a correlation with the incidence of seizures in epilepsy patients at Soebandi Hospital Jember.

The Effects of Cannabidiol on Canine Epilepsy and Arthritis – a Case Study

Cannabidiol oil (CBD) has gained notoriety in recent years due to its effectiveness as an adjuvant therapy in many pathologies.The purpose of this study is to evaluate the effects of CBD in the management of pain and the associated pathologies of epilepsy and arthritis, on a single subject, a female Labrador, 12.5 years old at the beginning of the study. The therapeutic protocol used was the administration of CBD oil, sublingually, in doses of 2.25 mg/kg/day. Hematology and biochemistry were performed at 3, 6 and 12 months. Radiology was performed before the study began and after 6 months.After the first month, a decrease in the number and severity of epilepsy crises was observed. Beginning with the first 2 weeks of CBD oil administration, the patient was already experiencing an improvement in her mobility along with general pain remittance and the amelioration of her 3rd degree lameness, quantified by the Colorado Pain Scale. After 5 months of CBD administration, with no seizures recorded, phenytoin therapy was ceased. After 8 months, phenobarbital was also excluded from the therapeutic protocol, thus making CBD an independent the rapeutic molecule. CBD appears to be a useful molecule in managing both pain and epilepsy.

On-Cell Stability for Therapeutic Drug Monitoring

Abstract Introduction A common problem in many clinical laboratories and outpatient clinics is processing specimens rapidly to comply with specimen stability criteria. Labs receive thousands of samples a day and may face challenges with staffing, equipment malfunction, or workflow, which can prevent immediate processing of samples. Currently, for therapeutic drug monitoring, the lab is required to centrifuge specimens and remove the serum/plasma from cells within 2-hours (CLSI-GP44-A4). Many of these drugs are monitored in the outpatient setting, which may require longer transportation times to get specimens from the collection location to the laboratory. This creates challenges for the lab in processing samples within 2-hours and may result in unnecessary rejection of otherwise acceptable specimens. Not all clinical sites have the staffing or space to process the specimens on site. Our objective was to determine if the on-cell stability of therapeutic drugs can be extended to beyond two hours. Methods We performed spiking studies to determine the on-cell stability of phenytoin in whole blood that was collected from healthy donors in barrier-free red top tubes. Phenytoin was spiked into the whole blood at a final concentration of about 10 (therapeutic) or 40 (toxic) µg/mL. The spiked whole blood samples were mixed by inverting six times and then were left at ambient temperature for 30 minutes, 2-, 4-, 6-, or 12-hours, after which they were centrifuged, and the serum was removed for analysis of total phenytoin concentration on the Abbott Architect and free and total phenytoin on the Beckman AU (n=3 per time point and concentration). In vivo studies are ongoing for an extended list of therapeutic drugs, in which two extra red top tubes are collected from patients being monitored for phenytoin, valproic acid, digoxin, vancomycin, lithium, or carbamazepine therapy. The two study tubes are kept at ambient temperature for 6- or 12-hours after collection before being centrifuged and separated from cells. The 6- and 12-hour drug concentrations were compared to the patient’s standard of care tube that was processed within 2-hours, after clotting for 30 minutes. Results Spiking studies demonstrated phenytoin was stable on cells for at least 12-hours at both 10 and 40 µg/mL. The percent total phenytoin remaining at 12-hours relative to the 30-minute control was 104 ± 2% at 10 µg/mL and 99 ± 16% at 40 µg/mL. Furthermore, the fraction of free phenytoin did not change over the 12 hours (10 µg/mL: 8 ± 1% free; 40 µg/mL: 10 ± 1% free). Our preliminary in vivo studies have shown no change in vancomycin or lithium concentration in samples processed 6- and 12-hours post-collection. Conclusion We have demonstrated that phenytoin, vancomycin, and lithium collected in red-top tubes are stable on cells at ambient temperature for at least 12-hours.

Does long-term phenytoin have a place in Dravet syndrome?

Anti-seizure medications that block sodium channels are generally considered contraindicated in Dravet syndrome. There is, however, considerable debate about the sodium-channel blocker phenytoin, which is often used for status epilepticus, a frequent feature of Dravet syndrome. We describe four patients with Dravet syndrome in whom long-term phenytoin therapy reduced seizure frequency and duration. In two patients, phenytoin produced prolonged periods without status epilepticus for the first time. Attempting to wean phenytoin in all patients after 1 to 20 years of use resulted in seizure exacerbation. Reintroducing phenytoin improved seizure control, suggesting phenytoin is beneficial in some patients with Dravet syndrome.

Paxlovid with Caution: Novel Case of Paxlovid-Induced Tacrolimus Toxicity in a Cardiac Transplant Patient.

Tacrolimus is commonly used as a prophylactic against acute rejection in transplant patients. Tacrolimus toxicity has numerous presentations that have been well documented in the literature and can be induced by a wide variety of agents. We present a novel case of tacrolimus toxicity in a cardiac transplant patient induced by outpatient treatment for COVID-19 pneumonia with ritonavir-nirmatrelvir, which was successfully treated with phenytoin therapy.LEARNING POINTSRitonavir-nirmatrelvir is a newly approved antiviral therapy for COVID-19 to prevent hospitalization and is increasingly prescribed in the outpatient setting.Thorough assessment of drug interactions prior to starting ritonavir-nirmatrelvir can prevent tacrolimus toxicity in patients with solid organ transplants.Phenytoin increases the metabolism of tacrolimus and can be safely utilized to treat tacrolimus toxicity.

Suplementasi asam folat untuk mengurangi pembesaran gingiva akibat terapi fenitoin: a scoping review

Background: Epilepsy is a neurological condition that around 70 million people worldwide have. Phenytoin is the most common anti-epileptic therapy for controlling epilepsy and preventing its recurrence. The side effect of phenytoin therapy includes gingival overgrowth which often causes psychological and aesthetical problems, interferes with normal mastication, and worsen the gingival inflammation. There are surgical and non-surgical options to treat phenytoin-induced gingival overgrowth, one of the non-surgical options to treat phenytoin-induced gingival overgrowth. One of the non-surgical treatment for phenytoin-induced gingival overgrowth is folic acid supplementation, which has been studied to prevent the adverse side effects of phenytoin therapy despite the variative results. Objective: To discover the current theory depiction about the effect of folic acid supplementation on gingival overgrowth due to phenytoin therapy. Method: The type of the research is descriptive observational research and method of scoping review. Journals obtained using PCC (population, concept, and context) with population of patients on phenytoin therapy, using concept of preventing phenytoin-induced gingival overgrowth using agent supplementation, and context of folic acid. The inclusion and exclusion criteria filtered by boolean search on two databases, PubMed and Google Scholar from 1987 to 2020. Results: A total of 5 journals found and all of them are included in a table with the results of the studies discussing about folic acid supplementation in phenytoin-induced gingival overgrowth. Conclusion: Folic acid supplementation was found to delay the onset, reduce the incidence and severity as well as the risk of recurrence after gingivectomy on phenytoin-induced gingival overgrowth.

Cutaneous Adverse Drug Reactions

An adverse drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A cutaneous eruption is one of the most common manifestations of an adverse drug reaction. This chapter reviews the epidemiology, etiology, diagnosis, clinical manifestations, and differential diagnosis of adverse drug reactions, as well as laboratory tests for them. Also discussed are the types of cutaneous eruption: exanthematous eruption, urticarial eruption, blistering eruption, pustular eruption, and others. The simple and complex forms of each type of eruption are reviewed. The chapter includes 4 tables and 12 figures. Tables present the warning signs of a serious drug eruption, clinical features of hypersensitivity syndrome reaction and serum sickness-like reaction, characteristics of Stevens-Johnson Syndrome and toxic epidermal necrolysis, and clinical pearls to identify anticoagulant-induced skin necrosis. Figures illustrate hypersensitivity syndrome reaction, a fixed drug eruption from tetracycline, pseudoporphyria from naproxen, linear immunoglobulin A disease induced by vancomycin, pemphigus foliaceus from taking enalapril, pemphigus vulgaris from taking penicillamine, toxic epidermal necrolysis after starting phenytoin therapy, acneiform drug eruption due to gefitinib, acute generalized exanthematous pustulosis from cloxacillin, coumarin-induced skin necrosis, a lichenoid drug eruption associated with ramipril, and leukocytoclastic vasculitis from hydrochlorothiazide. This chapter contains 106 references.

Cutaneous Adverse Drug Reactions

An adverse drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A cutaneous eruption is one of the most common manifestations of an adverse drug reaction. This chapter reviews the epidemiology, etiology, diagnosis, clinical manifestations, and differential diagnosis of adverse drug reactions, as well as laboratory tests for them. Also discussed are the types of cutaneous eruption: exanthematous eruption, urticarial eruption, blistering eruption, pustular eruption, and others. The simple and complex forms of each type of eruption are reviewed. The chapter includes 4 tables and 12 figures. Tables present the warning signs of a serious drug eruption, clinical features of hypersensitivity syndrome reaction and serum sickness-like reaction, characteristics of Stevens-Johnson Syndrome and toxic epidermal necrolysis, and clinical pearls to identify anticoagulant-induced skin necrosis. Figures illustrate hypersensitivity syndrome reaction, a fixed drug eruption from tetracycline, pseudoporphyria from naproxen, linear immunoglobulin A disease induced by vancomycin, pemphigus foliaceus from taking enalapril, pemphigus vulgaris from taking penicillamine, toxic epidermal necrolysis after starting phenytoin therapy, acneiform drug eruption due to gefitinib, acute generalized exanthematous pustulosis from cloxacillin, coumarin-induced skin necrosis, a lichenoid drug eruption associated with ramipril, and leukocytoclastic vasculitis from hydrochlorothiazide. This chapter contains 106 references.

Cutaneous Adverse Drug Reactions

An adverse drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A cutaneous eruption is one of the most common manifestations of an adverse drug reaction. This chapter reviews the epidemiology, etiology, diagnosis, clinical manifestations, and differential diagnosis of adverse drug reactions, as well as laboratory tests for them. Also discussed are the types of cutaneous eruption: exanthematous eruption, urticarial eruption, blistering eruption, pustular eruption, and others. The simple and complex forms of each type of eruption are reviewed. The chapter includes 4 tables and 12 figures. Tables present the warning signs of a serious drug eruption, clinical features of hypersensitivity syndrome reaction and serum sickness-like reaction, characteristics of Stevens-Johnson Syndrome and toxic epidermal necrolysis, and clinical pearls to identify anticoagulant-induced skin necrosis. Figures illustrate hypersensitivity syndrome reaction, a fixed drug eruption from tetracycline, pseudoporphyria from naproxen, linear immunoglobulin A disease induced by vancomycin, pemphigus foliaceus from taking enalapril, pemphigus vulgaris from taking penicillamine, toxic epidermal necrolysis after starting phenytoin therapy, acneiform drug eruption due to gefitinib, acute generalized exanthematous pustulosis from cloxacillin, coumarin-induced skin necrosis, a lichenoid drug eruption associated with ramipril, and leukocytoclastic vasculitis from hydrochlorothiazide. This chapter contains 106 references.

Efficiency of topical phenytoin in diabetic foot ulcer care: A randomized control trial

Aim: To study the efficiency of topical phenytoin on healing in diabetic foot ulcer grades 1 and 2. Methods: Totally, 60 patients in each group with diabetic foot ulcers of more than 4 weeks duration without any co-morbid conditions and ulcers belonging to Grade 1 and 2 as per Meggitt – Wagner’s diabetic foot ulcers were inducted into the study. The whole sample population was divided into two equal and comparable groups based on willingness for undergoing topical phenytoin therapy for the wound. Those who were not willing were subjected to conventional wound care, forming the control group. Antibiotics are given to both groups as per culture reports. Results: In the study group, 13 patients had granulation tissue at 14 days of less than 75%, and 17 patients had granulation tissue at 14 days of greater than 75%. In the control group mean value of the size of the ulcer initially is 8.76cm and in 7 days is 7.12 cm and in 14 days is 5.86 cm. In the study group mean value of the size of the ulcer initially is 9.03 cm and in 7 days is 5.63 cm and in 14days is 3.3 cm. Conclusion: Phenytoin enhances wound healing via the following mechanisms: stimulation of fibroblast proliferation, enhancement of granulation tissue development, and inhibition of collagenase activity.

Use of Saliva as an Alternative Matrix to Serum/Plasma for Therapeutic Drug Monitoring Using Reverse-Phase HPLC

This study was conducted to examine and verify the use of saliva as an alternative matrix for monitoring phenytoin drug levels in patients with epilepsy. Drug concentrations are measured to evaluate whether a suitable drug level has been achieved to minimize the risk for toxicity, inadequate efficacy, or therapy resistance and compliance issues. Quantitative analysis was performed by using reverse-phase HPLC after sample pretreatment with acetonitrile. Seventy-eight patients who met the inclusion/exclusion criteria were examined in this study. Trough concentrations of both saliva and serum were taken at steady state. Of the 78 patients enrolled, only 11 (14.1%) had normal levels. Twenty-eight patients (35.9%) had subtherapeutic levels, and 39 (50%) had toxic levels. Simultaneously, salivary phenytoin levels were analyzed; only 13 patients (17.3%) had therapeutic levels, 25 patients (33.3%) had subtherapeutic levels, and 37 (49.3%) had toxic levels. Among the study population, most of the patients were aged 31 to 40 years (25.6%) followed by the age group 21 to 30 years (19.2%). The lowest percentage of patients were in the age groups 71 to 80 years and >80 years (1.3%) each. This study found a statistically significant relationship between free serum and salivary phenytoin levels (P < 0.001). A very weak and insignificant correlation was observed between serum/salivary phenytoin levels and sex/age of the study population. The results of the present study support the use of saliva as an alternative to serum/plasma for monitoring phenytoin therapy. The free concentration of a drug represents the freely diffusible drug fraction, which is the therapeutically active form. Accordingly, the free drug concentration correlates to clinical efficacy and drug toxicity better than total concentration.