phenytoin (Rx)

Brand and Other Names:Dilantin, Dilantin 125, more...Phenytek
  • Print

Dosing & Uses


Dosage Forms & Strengths

capsule, immediate-release

  • 30mg
  • 100mg

capsule, extended-release

  • 100mg
  • 200mg
  • 300mg

tablet, chewable

  • 50mg

oral suspension

  • 125mg/5mL

injectable solution

  • 50mg/mL


Status epilepticus

  • Load 10-15 mg/kg or 15-20 mg/kg at 25-50 mg/min, THEN  
  • Maintenance: 100 mg IV/PO q6-8hr PRN
  • Administer IV slowly; not to exceed 50 mg/min


  • Tablet
    • 100 mg PO TID
    • Maintenance: 300-400 mg/day; increase to 600 mg/day if necessary
    • May adjust dose no sooner than 7-10 day intervals when indicated
  • Suspension
    • 125 mg PO TID, initially
    • Increase to 625 mg/day if necessary
    • May adjust dose no sooner than 7-10 day intervals when indicated
  • Extended release
    • Loading dose: 1 g divided into 3 doses (400, 300, 300 mg) administered at 2 hr intervals; initiate dosage 24 hr after loading dose
    • Loading dose not for administration to patients with a history of renal or hepatic disease; reserve for patients who require rapid steady serum levels, when IV administration not desirable, and for patients in a clinic or hospital setting where phenytoin levels can be closely monitored
    • Treatment (naive): 100 mg PO TID initially
    • May adjust dose no sooner than 7-10 day intervals
  • Therapeutic range: 10-20 mcg/mL (total) or 1-2 mcg/mL free drug

Dosage Forms & Strengths

capsule, immediate-release

  • 30mg
  • 100mg

capsule, extended-release

  • 100mg
  • 200mg
  • 300mg


  • 50mg

oral suspension

  • 125mg/5mL

injectable solution

  • 50mg/mL

Status Epilepticus

15-20 mg/kg IV in single or divided dose; if necessary may administer additional dose of 5-10 mg/kg 10 min after loading dose  

Maintenance: 4-8 mg/kg/day IV divided twice daily

Control of Tonic-Clonic and Complex Partial Seizures

Initial dosage

  • Neonates: 5 mg/kg/day in 2 divided doses  
  • 6 months to 16 years: 5 mg/kg/day in 2-3 divided doses

Neonates (<28 days)

  • Initial: 5-8 mg/kg/day IV/PO divided q8-12hr

Age-based maintenance dose

  • 6 months-4 years: Usual range, 8-10 mg/kg/day IV/PO divided two to three times daily
  • 4-7 years: Usual range, 7.5-9 mg/kg/day IV/PO divided two to three times daily
  • 7-10 years: Usual range, 7-8 mg/kg/day IV/PO divided two to three times daily
  • 10-16 years: Usual range, 6-7 mg/kg/day IV/PO divided two to three times daily

Anticonvulsant (Nonemergent)

Children and adolescents

Immediate release

  • Tablet and suspension
  • 5 mg/kg/day PO in 2-3 divided doses, initially; may make dose adjustments no sooner than 7-10 day intervals
  • Maintenance: 4-8 mg/kg/day PO; not to exceed 300 mg/day; higher doses may be considered in infant and young children (range: 8-10 mg/kg/day in divided doses)

Extended release

  • 5 mg/kg/day PO, initially in 2-3 equally divided doses; may adjust dose no sooner than 7-10-day intervals  
  • Maintenance: 4-8 mg/kg/day PO not to exceed 300 mg/day

Dosing Considerations

<6 years: Potential toxic dose, 20 mg/kg

Therapeutic range: 10-20 mcg/mL (total) or 1-2 mcg/mL free drug

ALWAYS administer IV slowly; not to exceed 1-3 mg/kg/min



Interaction Checker

and phenytoin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found


      Serious - Use Alternative

        Significant - Monitor Closely


            All Interactions Sort By:
             activity indicator 

            Adverse Effects

            Frequency Not Defined







            Slurred speech









            Gingival hyperplasia (pediatric patients)


            Paradoxical seizure

            Drug withdrawal seizure


            Psychosis (high dose)

            Toxic amblyopia


            AV conduction disorder

            Ventricular fibrillation





            Megaloblastic (folate-deficiency) anemia





            Purple glove syndrome


            Allergic reactions in the form of rash or, rarely, more serious forms (drug reaction with eosinophilia and systemic symptoms, or DRESS) or anaphylaxis

            Purpuric rash

            Toxic epidermal necrolysis

            Bullous, exfoliative, or purpuric dermatitis

            Coarsening of facial features

            Periarteritis nodosa

            Immunoglobulin abnormalities

            Altered taste sensation, including metallic taste

            Peyronie disease

            IV >50 mg/min

            • CNS depression
            • Cardiovascular collapse
            • Hypotension


            • Dyskinesia
            • Ophthalmoplegia
            • Nephrotoxicity
            • Stevens-Johnson syndrome
            • Lupus erythematosus
            • Rickets
            • Osteomalacia

            Postmarketing Reports

            Cerebellar atrophy


            Generalized exanthematous pustulosis




            Black Box Warnings

            Cardiovascular risk associated with rapid infusion rates

            • Risk of hypotension and arrhythmias with infusion rates that exceed 50 mg/min in adults and 1-3 mg/kg/min (or 50 mg/min, whichever is slower) for pediatric patients
            • Careful cardiac monitoring is needed during and after IV administration
            • These events have also been reported at or below 50 mg/min
            • Reduce infusion rate or discontinuation may be needed



            Sinus bradycardia

            Sinoatrial block

            Second and third degree A-V block

            Adams-Stokes syndrome

            Concurrent use with delavirdine

            History of prior acute hepatotoxicity attributable to phenytoin


            Erratically absorbed when administered IM, so this route should be used as a last resort

            ONLY extended-release capsules should be used for once-daily dosing regimens

            Decreased bone mineral density reported with chronic use

            Rapid intravenous administration increases the risk of adverse cardiovascular reactions, including severe hypotension and cardiac arrhythmias; in pediatric patients, administer the drug at a rate not exceeding 1 to 3 mg/kg/min or 50 mg per minute, whichever is slower; although risk of cardiovascular toxicity increases with infusion rates above recommended infusion rate, these events have also been reported at or below recommended infusion rate

            May cause fetal harm when administered to a pregnant woman

            Phenytoin induces hepatic metabolizing enzymes, which may enhance metabolism of vitamin D and decrease vitamin D levels, leading to vitamin D deficiency, hypocalcemia, and hypophosphatemia; consideration should be given to screening with bone-related laboratory and radiological tests as appropriate and initiating treatment plans according to established guidelines

            Use caution in cardiovascular disease, hypoalbuminemia, hepatic impairment, hypothyroidism, or seizures; because fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients

            Associated with exacerbation of porphyria; exercise caution when used in patients with this disease

            Extensively bound to serum plasma proteins and is prone to competitive displacement

            Acute alcoholic intake may increase phenytoin serum levels, while chronic alcoholic use may decrease serum levels

            Risk of hypotension and arrhythmias with infusion rates that exceed 50 mg/min in adults and 1-3 mg/kg/min (or 50 mg/min, whichever is slower) for pediatric patients

            Hematologic effects reported with use including agranulocytosis, leukopenia, pancytopenia, neutropenia, thrombocytopenia, and anemias

            Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes

            Increased risk of suicidal thoughts or behavior reported

            May render OCPs ineffective because of induction of hepatic metabolism

            Risk of gingival hyperplasia

            Local toxicity (purple glove syndrome) that includes edema, discoloration, and pain distal to the site of injection has been reported following peripheral IV injection; may or may not be associated with extravasation; this syndrome may not develop for several days after injection

            IV infusion not recommended by many due to poor solubility and risk of crystal formation; others state it is doable with right solvent and concentration

            Good for automatic and reentrant arrhythmias, not PSVT's

            Phenytoin was listed by the FDA as one of the drugs to monitor after having identified potential signs of serious risks or new safety information in the agency's Adverse Event Reporting System (AERS) database during the last 3 months of 2011

            Drug interactions resulting in decreased effectiveness of nondepolarizing neuromuscular blocking agents have been reported

            The FDA has not suggested that clinicians stop prescribing any drugs on the watch list or that patients stop taking them; it has, however, advised that patients with questions about watch-list drugs discuss them with their clinician

            Antiepileptic drugs should not be abruptly discontinued because of the possibility of increased seizure frequency, including status epilepticus

            Hyperglycemia, resulting from drug's inhibitory effect on insulin release reported; phenytoin may also raise serum glucose level in patients diabetes mellitus; use caution

            Not indicated for seizures resulting from hypoglycemia or other metabolic causes; appropriate diagnostic procedures should be performed as indicated

            Not effective for absence seizures; if tonic-clonic and absence seizures present, combined drug therapy needed

            Sustained serum levels of phenytoin above optimal range may produce confusional states referred to as "delirium", "psychosis", or "encephalopathy", or rarely irreversible cerebellar dysfunction; accordingly, at the first sign of acute toxicity, plasma levels are recommended; dose reduction of phenytoin therapy is indicated if plasma levels are excessive; termination recommended if symptoms persist

            The lethal dose in pediatric patients is not known; in adults, the lethal dose is estimated to be 2- 5 g; initial symptoms include nystagmus, ataxia, and dysarthria; other signs are tremor, hyperreflexia, lethargy, slurred speech, blurred vision, nausea, and vomiting; death is due to respiratory and circulatory depression

            Phenytoin may decrease serum concentrations of thyroid hormone (T4 and T3), sometimes with an accompanying increase in thyroid-stimulating hormone (TSH), but usually in absence of clinical hypothyroidism

            Cases of bradycardia and cardiac arrest reported, both at recommended phenytoin doses and levels, and in association with phenytoin toxicity; most reports of cardiac arrest occurred in patients with underlying cardiac disease

            Angioedema reported with phenytoin and fosphenytoin; discontinue immediately if symptoms of angioedema (eg, facial, perioral, or upper airway swelling) occur

            Metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19, and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism; if metabolism inhibited, may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity

            Patients with decreased CYP2C9 function

            • Patients who are intermediate or poor metabolizers of CYP2C9 substrates (eg, *1/*3, *2/*2, *3/*3) may exhibit increased phenytoin serum concentrations compared to patients who are normal metabolizers (eg, *1/*1); patients who are known to be intermediate or poor metabolizers may ultimately require lower doses to maintain similar steady-state concentrations compared to normal metabolizers
            • In patients who are known to be carriers of the decreased function CYP2C9*2 or *3 alleles (intermediate and poor metabolizers), consider starting at the low end of the dosage range and monitor serum concentrations to maintain total phenytoin concentrations of 10 to 20 mcg/mL; if early signs of dose-related central nervous system (CNS) toxicity develop, serum concentrations should be checked immediately

            Severe cutaneous reactions

            • Can cause severe cutaneous adverse reactions (SCARs), which may be fatal
            • Reported reactions include toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
            • Onset is usually within 28 days, but can occur later
            • Discontinue at the first sign of a rash, unless the rash is clearly not drug-related
            • If signs or symptoms suggest a severe cutaneous adverse reaction, do not resume drug; consider alternant therapy
            • Studies in patients of Chinese ancestry have found a strong association between risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene in patients taking carbamazepine
            • Limited evidence suggests that HLA-B*1502 or CYP2C9*3 may also be a risk factor for the development of SJS/TEN in patients taking other antiepileptic drugs
            • DRESS
              • DRESS, also known as multiorgan hypersensitivity, reported in patients taking antiepileptic drugs, including phenytoin and fosphenytoin
              • Some of these events have been fatal or life-threatening
              • DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection); eosinophilia is often present
              • Early manifestations of hypersensitivity (eg, fever or lymphadenopathy) may be present even though rash is not evident
              • If such signs or symptoms are present, evaluate patient immediately; discontinue drug if unable to confirm other etiology for the rash

            Pregnancy & Lactation

            Pregnancy: Pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as phenytoin, during pregnancy is available; pregnant patients taking should enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334; it must be done by patients themselves; Information on the registry can also be found at the website

            An increased incidence of major malformations (such as orofacial clefts and cardiac defects) and abnormalities characteristic of fetal hydantoin syndrome (dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities [including microcephaly], and cognitive deficits) reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy

            An increase in seizure frequency may occur during pregnancy; periodic measurement of plasma phenytoin concentrations may be valuable to make appropriate dosage adjustments; postpartum restoration of original dosage will probably be indicated

            Consider vitamin K supplementation for 1 month before birth

            Lactation: Phenytoin is secreted in human milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from phenytoin or from underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.



            Mechanism of Action

            Promotes Na+ efflux or decreases Na+ influx from membranes in motor cortex neurons; stabilizes neuronal membrane

            Slows conduction velocity


            Bioavailability: May vary between different manufacturers; dependent on formulation

            Onset: 1 week (PO); 2-24 hr (PO with loading dose); 0.5-1 hr (IV)

            Peak plasma time: 1.5-3 hr (immediate-release); 4-12 hr (extended-release)


            Protein bound: 95% (adults); 85% (infants); 80% (neonates)

            Vd: 0.6-0.7 L/kg (adults); 0.7 L/kg (children); 0.7-0.8 L/kg (infants); 0.8-0.9 L/kg (full-term neonate); 1-1.2 L/kg (premature neonate)


            Metabolized by hepatic P450 enzyme CYP2C9

            Metabolites: Inactive

            Enzymes induced: CYP3A4


            Half-life: 22 hr (PO); 10-15 hr (IV)

            Excretion: Urine


            HLA variants

            • Patients with HLA-B*1502 with are more likely to have a severe dermatologic reaction (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome) when taking phenytoin
            • This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais

            Epoxide genotypes

            • Maternal epoxide (EPHX1) genotypes 113*H and 139*R are associated with risk of fetal hydantoin syndrome among pregnant women taking phenytoin
            • Increased levels of the reactive epoxide metabolites by either inhibiting the detoxification of these metabolites by epoxide hydrolase or by increasing conversion to epoxide metabolites by inducing CYP3A4, 2C9, or 2C19

            Genetic testing laboratories (for HLA variants)

            • Kashi Clinical Laboratories (
            • LabCorp (
            • Specialty Laboratories (
            • Quest (


            IV Incompatibilities


            • D5/NS
            • D5W
            • LR
            • 1/2NS
            • NS(?)


            • Amikacin
            • Bretylium
            • Dobutamine
            • Hydroxyzine
            • Insulin (regular)
            • Levorphanol, lidocaine, lincomycin
            • Meperidine, metaraminol, morphine sulfate
            • Nitroglycerin, norepinephrine
            • Pentobarbital, procaine
            • Streptomycin


            • Hydromorphone
            • Sufentanil


            • Ampho B cholesteryl sulfate, ciprofloxacin, clarithromycin, diltiazem, enalaprilat, fenoldopam, fentanyl, gatifloxacin, heparin, heparin/hydrocortisone, hydromorphone, linezolid, methadone, morphine sulfate, KCl, propofol, sufentanil, theophylline, vitamins B/C

            IV Compatibilities


            • Verapamil


            • Esmolol
            • Famotidine
            • Fluconazole
            • Foscarnet
            • Tacrolimus

            IV Preparation

            Load IV in 250 mL NS; monitor BP

            Further dilution of IV infusion solution is controversial, and no consensus exists as to optimal concentration and length of stability

            Stability is concentration and pH dependent

            Based on limited clinical consensus, NS and LR are recommended diluents; dilutions of 1-10 mg/mL have been used and should be administered ASAP after preparation

            IV/IM Administration

            Administer slowly; no more than 50 mg/min in adults and no more than 1-3 mg/kg/min in pediatric patients

            IM: Although approved for IM use, IM administration is not recommended, due to erratic absorption and pain on injection; fosphenytoin may be considered

            IV: IV infusion not recommended


            Store intact vials at room temperature; protect from freezing

            If refrigerated, ppt forms, but dissolves on standing at room temp; OK for use





            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient



            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient



            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.