fosphenytoin (Rx)

Brand and Other Names:Cerebyx, Sesquient
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • Cerebyx, Sesquient, generic
    • 100mg PE/2mL
    • 500mg PE/10mL

Status Epilepticus

Cerebyx, Sesquient, generic

Indicated for treatment of generalized tonic-clonic status epilepticus

Loading dose: 15-20 mg PE/kg IV at a rate of 100-150 mg PE/min, not to exceed 150 mg PE/min  

Owing to full antiepileptic effect of phenytoin is not immediate, other measures, including coadministration of an IV benzodiazepine, may be necessary for the control of status epilepticus

If seizures continues after administration, consider using other anticonvulsants and other appropriate measures

If IV access is unavailable, loading doses have been given by IM route

Nonemergent Seizures

Cerebyx, Sesquient, generic

Indicated for prevention and treatment of seizures occurring during neurosurgery

Also, indicated for short-term substitution for oral phenytoin; only when oral phenytoin administration is not possible

Loading dose: 10-20 mg PE/kg IV; not to exceed 150 mg PE/min

Maintenance dose: 4-6 mg PE/kg/day IV in divided doses IV, not to exceed 150 mg PE/min

Individualize subsequent maintenance doses by monitoring serum concentrations to achieve a target therapeutic concentration

Owing to risks of cardiac and local toxicity associated with IV administration, oral phenytoin should be used whenever possible

Dosage Modifications

Renal or renal impairment

  • Patients with renal or hepatic disease, or in those with hypoalbuminemia may have an increase amount of unbound phenytoin (active metabolite); monitor phenytoin serum levels based on the unbound fraction
  • After IV administration to patients with renal and/or hepatic disease, or hypoalbuminemia, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance; may potentiate the frequency and severity of adverse events

Dosing Considerations

Use caution when administering owing to the risk of dosing errors

Phenytoin sodium equivalents (PE)

  • Express dose, concentration, and infusion rate of fosphenytoin as phenytoin sodium equivalents (PE) when prescribing
  • No need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses

Concentration of 50 mg PE/mL

  • Do not confuse the concentration of fosphenytoin with the total amount of drug in the vial
  • Errors, including fatal overdoses, have occurred when vial concentration (50 mg PE/mL) was misinterpreted to mean that the total content of the vial was 50 mg PE
  • These errors have resulted in 2-10 fold overdoses since each of the vials actually contains a total of 100 mg PE (2-mL vial) or 500 mg PE (10-mL vial)
  • Ensure appropriate volume is withdrawn from vial when preparing dose

Monitoring parameters

  • Continually monitor electrocardiogram, blood pressure, and respiratory function
  • Observe patient throughout period where maximal serum phenytoin concentrations occur (~10-20 min after infusion ended)

Dosage Forms & Strengths

injectable solution

  • Cerebyx, Sesquient, generic
    • 100mg PE/2mL
    • 500mg PE/10mL

Status Epilepticus

Cerebyx, generic

Indicated for treatment of generalized tonic-clonic status epilepticus

Owing to full antiepileptic effect of phenytoin is not immediate, other measures, including coadministration of an IV benzodiazepine, may be necessary for the control of status epilepticus

If seizures continues after administration, consider using other anticonvulsants and other appropriate measures

If IV access is unavailable, loading doses have been given by IM route

Birth to <17 years

  • Loading dose: 15-20 mg PE/kg IV at a rate of 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower)  

≥17 years

  • Loading dose: 15-20 mg PE/kg IV at a rate of 100-150 mg PE/min, not to exceed 150 mg PE/min  

Nonemergent Seizures

Cerebyx: Indicated for prevention and treatment of seizures occurring during neurosurgery

Cerebyx, Sesquient: Also, indicated for short-term substitution for oral phenytoin; only when oral phenytoin administration is not possible

Individualize subsequent maintenance doses by monitoring serum concentrations to achieve a target therapeutic concentration

Owing to risks of cardiac and local toxicity associated with IV administration, oral phenytoin should be used whenever possible

Birth to <17 years (Cerebyx, generic)

  • Loading dose: 10-15 mg PE/kg IV; 1-2 PE/kg/min, or 150 mg PE/min, whichever is slower
  • Maintenance dose
    • 2-4 mg PE/kg/day IV in q12hr divided doses initially, THEN
    • 4-8 mg PE/kg/day IV in q12hr divided doses
    • At a rate of 1-2 mg PE/kg/min (or 100 mg PE/min, whichever is slower)

≥17 years (Cerebyx)

  • Loading dose: 10-15 mg PE/kg IV; not to exceed 150 mg PE/min
  • Maintenance dose: 4-6 mg PE/kg/day IV in divided doses, not to exceed 150 mg PE/min

2-17 years (Sesquient)

  • <2 years: Safety and efficacy not established
  • >2 years
    • Loading dose: 10-15 mg PE/kg IV; not to exceed 0.4 mg PE/kg/min
    • 2-4 mg PE/kg IV in q12hr divided doses initially, THEN
    • 4-8 PE/kg/day IV in q12hr divided doses
    • Because of the betadex sulfobutyl ether sodium ingredient in Sesquient, do not exceed administration rate in pediatric patients of 0.4 mg PE/kg/min

Dosage Modifications

Renal or renal impairment

  • Patients with renal or hepatic disease, or in those with hypoalbuminemia may have an increase amount of unbound phenytoin (active metabolite); monitor phenytoin serum levels based on the unbound fraction
  • After IV administration to patients with renal and/or hepatic disease, or hypoalbuminemia, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance; may potentiate the frequency and severity of adverse events

Dosing Considerations

Use caution when administering owing to the risk of dosing errors

Phenytoin sodium equivalents (PE)

  • Express dose, concentration, and infusion rate of fosphenytoin should always be expressed as phenytoin sodium equivalents (PE) when prescribing
  • No need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses

Concentration of 50 mg PE/mL

  • Do not confuse the concentration of fosphenytoin with the total amount of drug in the vial
  • Errors, including fatal overdoses, have occurred when vial concentration (50 mg PE/mL) was misinterpreted to mean that the total content of the vial was 50 mg PE
  • These errors have resulted in 2-10 fold overdoses since each of the vials actually contains a total of 100 mg PE (2-mL vial) or 500 mg PE (10-mL vial)
  • Ensure appropriate volume is withdrawn from vial when preparing dose

Monitoring parameters

  • Continually monitor electrocardiogram, blood pressure, and respiratory function
  • Observe patient throughout period where maximal serum phenytoin concentrations occur (~10-20 min after infusion ended)
  • Usual therapeutic serum total phenytoin concentration 10-20 mcg/mL (unbound phenytoin concentration [1-2 mcg/mL])
  • Recommended to not monitor until conversion to phenytoin is complete (~2 hr after end of IV infusion and ~4 hr after IM administration)
Next:

Interactions

Interaction Checker

and fosphenytoin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Adults and children

            • Body as a whole: Fever, injection-site reaction, infection, chills, face edema, injection-site pain
            • Cardiovascular: Hypertension
            • Digestive: Constipation
            • Metabolic and nutritional: Hypokalemia
            • Musculoskeletal: Myasthenia; Infrequent: myopathy, leg cramps, arthralgia, myalgia
            • Nervous: Reflexes increased, speech disorder, dysarthria, intracranial hypertension, thinking abnormal, nervousness
            • Respiratory: Pneumonia
            • Skin and appendages: Rash

            IV, adults

            • Pruritus (49%)
            • Nystagmus (44%)
            • Dizziness (31%)
            • Somnolence (20%)
            • Ataxia (11%)

            IV, children and adolescents

            • Vomiting (21%)
            • Nystagmus (18%)

            IM

            • Nystagmus (15%)

            1-10%

            Adults and children

            • Body as a whole: Sepsis, injection-site inflammation, injection-site edema, injection-site hemorrhage, flu syndrome, malaise, generalized edema, shock, photosensitivity reaction, cachexia, cryptococcosis
            • Endocrine: Diabetes insipidus
            • Hematologic and lymphatic: Thrombocytopenia, anemia, leukocytosis, cyanosis, hypochromic anemia, leukopenia, lymphadenopathy, petechia
            • Metabolic and nutritional: Hyperglycemia, hypophosphatemia, alkalosis, acidosis, dehydration, hyperkalemia, ketosis
            • Musculoskeletal: Myopathy, leg cramps, arthralgia, myalgia
            • Nervous: Confusion, twitching, Babinski sign positive, circumoral paresthesia, hemiplegia, hypotonia, convulsion, extrapyramidal syndrome, insomnia, meningitis, depersonalization, CNS depression, depression, hypokinesia, hyperkinesia, paralysis, psychosis, aphasia, emotional lability, coma, hyperesthesia, myoclonus, personality disorder, acute brain syndrome, encephalitis, subdural hematoma, encephalopathy, hostility, akathisia, amnesia, neurosis
            • Skin and appendages: Maculopapular rash, urticaria, sweating, skin discoloration, contact dermatitis, pustular rash, skin nodule
            • Special senses: Visual field defect, eye pain, conjunctivitis, photophobia, hyperacusis, mydriasis, parosmia, ear pain, taste loss
            • Urogenital: Urinary retention, oliguria, dysuria, vaginitis, albuminuria, genital edema, kidney failure, polyuria, urethral pain, urinary incontinence, vaginal moniliasis

            IV, adults

            • Nausea (9%)
            • Tinnitus (9%)
            • Hypotension (8%)
            • Stupor (8%)
            • Vasodilatation (6%)
            • Pelvic pain (4%)
            • Tongue disorder (4%)
            • Dry mouth (4%)
            • Incoordination (4%)
            • Paresthesia (4%)
            • Extrapyramidal syndrome (4%)
            • Tremor (3%)
            • Agitation (3%)
            • Diplopia (3%)
            • Taste perversion (3%)
            • Amblyopia (2%)
            • Deafness (2%)
            • Hypesthesia (2%)
            • Dysarthria (2%)
            • Vertigo (2%)
            • Brain edema (2%)
            • Vomiting (2%)
            • Asthenia (2%)
            • Back pain (2%)
            • Headache (2%)

            IV, children and adolescents

            • Ataxia (10%)
            • Fever (8%)
            • Nervousness (7%)
            • Pruritus (6%)
            • Somnolence (6%)
            • Hypotension (5%)
            • Rash (5%)

            IM

            • Tremor (10%)
            • Headache (9%)
            • Asthenia (9%)
            • Ataxia (8%)
            • Incoordination (8%)
            • Somnolence (7%)
            • Dizziness (5%)
            • Nausea (5%)
            • Paresthesia (4%)
            • Reflexes decreased (3%)
            • Pruritus (3%)
            • Vomiting (3%)

            Postmarketing Reports

            Body as a whole: Anaphylaxis, angioedema

            Laboratory test abnormality: Decrease serum concentrations of T4; may also produce lower than normal values for dexamethasone or metyrapone tests; increase serum levels of gamma glutamyl transpeptidase

            Nervous system disorders: Dyskinesia

            Previous
            Next:

            Warnings

            Black Box Warnings

            Cardiovascular risk associated with rapid infusion rates

            • Risk of hypotension and arrhythmias with infusion rates that exceed 150 mg/minute of phenytoin sodium equivalents (PE)
            • Careful cardiac monitoring is needed during and after administering IV administration; these events have also been reported at or below 150 mg PE/minute
            • Recommended doses should not be changed when substituting fosphenytoin for phenytoin or vice versa; they are not equivalent on mg to mg basis
            • Reduce infusion rate or discontinuation may be needed

            Contraindications

            Hypersensitivity to or its inactive ingredients, or to phenytoin or other hydantoins

            Sinus bradycardia, sinoatrial block, 2nd or 3rd degree AV block, Adams-Stokes syndrome

            Prior history of acute hepatotoxicity attributable to fosphenytoin or phenytoin

            Coadministration with delavirdine

            Cautions

            Do NOT give IM for status epilepticus initial dose

            Renal, hepatic or other hypoalbuminemic disease: monitor unbound phenytoin concentration

            Do not abruptly discontinue antiepileptic drugs because of the possibility of increased seizure frequency, including status epilepticus; in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary

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

            Hyperglycemia, resulting from phenytoin’s inhibitory effect on insulin release, reported; phenytoin may also raise serum glucose concentrations in diabetic patients

            Do not discontinue antiepileptic drugs abruptly because of possibility of increased seizure frequency, including status epilepticus; reduce dose gradually when necessary; in the event of allergic or hypersensitivity reaction, rapid substitution of alternative therapy, not belonging to hydantoin chemical class is necessary

            Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, reported with phenytoin; discontinue and do not readminister if acute hepatotoxicity occurs

            Hematopoietic complications (eg, thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia with or without bone marrow suppression), some fatal, have occasionally been reported; in cases of lymphadenopathy, follow-up observation for an extended period is indicated

            Consider phosphate load (0.0037 mmol phosphate/mg PE fosphenytoin) when treating patients who require phosphate restriction, such as those with severe renal impairment

            Safety/efficacy not evaluated for administration > 5 days

            Consider alternatives to structurally similar drugs such as carboxamides (eg, carbamazepine), barbiturates, succinimides, and oxazolidinediones (eg, trimethadione) in patients who experienced phenytoin hypersensitivity

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

            Severe burning, itching, and/or paresthesia were reported; IV fosphenytoin at doses of 20 mg PE/kg at 150 mg PE/min are expected to experience discomfort of some degree; occurrence and intensity of discomfort can be lessened by slowing or temporarily stopping the infusion

            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

            May cause fetal harm when administered to pregnant females

            Small percentage of treated individuals have been shown to metabolize phenytoin slowly; slow metabolism may be caused by limited enzyme availability and lack of induction; if early signs of dose-related CNS toxicity develop, check serum levels immediately

            Hyperglycemia, resulting from inhibitory effect of phenytoin on insulin release, has been reported; phenytoin may also raise serum glucose concentrations in diabetic patients

            Serum levels of phenytoin (the active metabolite of fosphenytoin) sustained above therapeutic range may produce confusional states referred to as “delirium,” “psychosis,” or “encephalopathy,” or rarely, irreversible cerebellar dysfunction and/or cerebellar atrophy; at first sign of acute toxicity, check serum levels immediately; reduce dose if serum levels are excessive; discontinue therapy if symptoms persist

            Cardiovascular risk associated with rapid infusion

            • Rapid IV administration increases the risk of adverse cardiovascular reactions, including severe hypotension and cardiac arrhythmias (eg, bradycardia, heart block, QT prolongation, ventricular tachycardia, ventricular fibrillation); use oral phenytoin whenever possible
            • Carefully monitor cardiac and respiratory function and after IV administration; consider reducing rate or discontinuing dose

            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 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

            Dosing errors

            • Do not confuse amount of drug to be given in PE with concentration of drug in vial
            • Medication errors associated with fosphenytoin have resulted in wrong dose being administer

            Drug interaction overview

            • CYP2C9 and CYP2C19 substrate; potent inducer of hepatic drug-metabolizing enzymes
            • Extensively bound to human plasma proteins
            • Addition or withdrawal of these agents in patients on phenytoin therapy may require an dosage adjustment of the phenytoin to achieve optimal clinical outcome
            • Drugs that may increase phenytoin concentration
              • Antiepileptic drugs (ie, ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate)
              • Azoles (ie, fluconazole, ketoconazole, itraconazole, miconazole, voriconazole)
              • Antineoplastic agents (eg, capecitabine, fluorouracil)
              • Antidepressants (ie, fluoxetine, fluvoxamine, sertraline)
              • Gastric acid reducing agents (eg, H2 antagonists, omeprazole)
              • Sulfonamides (eg, sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole/trimethoprim)
              • Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin
              • Drugs highly bound to albumin could increase the unbound fraction of fosphenytoin
            • Drug that may decrease phenytoin serum levels
              • Antineoplastic agents, usually in combination (eg, bleomycin, carboplatin, cisplatin, methotrexate
              • Antiviral agents (eg, fosamprenavir, nelfinavir, ritonavir)
              • Antiepileptic drugs (eg, carbamazepine, vigabatrin)
              • Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. John wort, theophylline
              • Drugs that may either increase or decrease phenytoin serum levels H5
              • Antiepileptic drugs (eg, phenobarbital, valproate sodium, valproic acid)
            • Drugs that decrease efficacy by phenytoin
              • Azoles (eg, fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole)
              • Antineoplastic agents (eg, irinotecan, paclitaxel, teniposide)
              • Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin
              • Coadministration with NNRTIs may cause loss of virologic response and possible resistance to NNRTIs (eg, delavirdine)
              • Cisatracurium, pancuronium, rocuronium and vecuronium: resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents has occurred in patients chronically administered phenytoin; closely monitor for more rapid recovery from neuromuscular blockade than expected, and infusion rate requirements may be higher
              • Others: Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D
            • Drugs whose level is decreased by phenytoin
              • Antiepileptic drugs (eg, carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine)
              • Antilipidemic agents (eg, atorvastatin, fluvastatin, simvastatin)
              • Antiviral agents (eg, efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir)
              • Fosamprenavir: Phenytoin is coadministered with fosamprenavir alone may decrease the concentration of amprenavir (active metabolite); when phenytoin is coadministered with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir
              • Calcium channel blockers (eg, nifedipine, nimodipine, nisoldipine, verapamil)
              • Others: Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine
            • Drug/laboratory test interactions
              • Exercise caution when using immunoanalytical methods to measure serum phenytoin concentrations following administration
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Exposure of phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes

            Prenatal phenytoin exposure is associated with an increased incidence of major malformations, including orofacial clefts and cardiac defects

            In addition, the fetal hydantoin syndrome, a pattern of abnormalities including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits has been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy

            There have been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy

            Pregnancy exposure registry

            • Monitors pregnancy outcomes in women exposed to antiepileptic drugs during pregnancy
            • Advised to pregnant females to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334, and must be done by patients themselves
            • Information on the registry can also be found at http://www.aedpregnancyregistry.org/

            Animal data

            • Administration to pregnant animals resulted in an increased incidence of fetal malformations and other manifestations of developmental toxicity (including embryofetal death, growth impairment, and behavioral abnormalities) in multiple species at clinically relevant doses

            Clinical considerations

            • An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics
            • Consider periodic measurement of serum phenytoin concentrations to provide the appropriate dosage adjustment; postpartum restoration of original dosage may be necessary
            • A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin in utero; may be prevented with vitamin K administration to mother before delivery and to neonate after birth

            Lactation

            It is not known whether fosphenytoin is secreted in human milk

            Following administration of phenytoin, phenytoin is secreted in human milk

            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.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Converted to phenytoin after injection; stabilizes neuronal membranes and decrease seizure activity by increasing efflux or decreasin influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses

            Absorption

            Bioavailability (IM): Completely bioavailable

            Peak plasma concentration

            • IV: When administered by IV infusion, maximum plasma fosphenytoin concentrations are achieved at the end of the infusion
            • IM: Following IM administration, plasma concentration are lower but more sustained than IV due to time required for absorption of fosphenytoin from the injection site

            Peak plasma time

            • IM: ~30 minutes postdose

            Distribution

            Protein bound: ~95-99% to human plasma proteins, primarily albumin

            Vd: 4.3-10.8 L

            Metabolism

            Fosphenytoin is rapidly converted via hydrolysis to phenytoin; phenytoin is metabolized in the liver and forms metabolites.

            Elimination

            Half-life: ~ 15 min (conversion of fosphenytoin to phenytoin)

            Excretion: Not in urine

            Pharmacogenomics

            Patients with HLA-B*1502 with are more likely to have a severe dermatologic reaction (eg, TEN, 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

            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

            • The following companies provide genetic testing for HLA variants
            • Kashi Clinical Laboratories (www.kashilab.com)
            • LabCorp (http://www.labcorp.com/)
            • Specialty Laboratories (http://www.specialtylabs.com)
            • Quest (http://www.questdialgnotics.com)
            Previous
            Next:

            Administration

            IV Incompatibilities

            Y-site: fenoldopam, midazolam

            IV Preparation

            Dilute in D5W or NS to concentration of 1.5-25 mg PE/mL

            IV Administration

            Express all dosing in mg "phenytoin equivalents" (PE); 1 mg PE is equivalent to 1 mg phenytoin sodium

            Do not confuse the concentration with the total amount of drug in the vial

            IV infusion preferred route for emergent use and for pediatrics because of delayed absorption

            Maximum IV infusion rate

            • Adults (≥17 years): Not to exceed 150 mg PE/min
            • Birth to <17 years: 2 mg PE/kg/min (or 100 mg PE/min, whichever is slower)

            Monitor

            • Continuous monitoring of ECG, BP, and respiratory function essential; observe patient throughout the period where maximal serum phenytoin concentrations occur, ~10-20 min after the end of infusions
            • Phenytoin levels: Obtain 2 hr after IV or 4 hr after IM

            Storage

            Unused vials

            • Cerebyx, generic: Refrigerate at 2-8ºC (36-46ºF); do not store at room temperature for more than 48 hr
            • Sesquient: Store at room temperature 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86∫F)
            • Vials that develop particulate matter should not be used
            • After opening, discard any unused solution in vials

            Diluted infusions

            • Stable at 1, 8, and 20 mg PE/mL in normal saline or D5W at 25ºC (77ºF) for 30 days in glass container and at 4-20ºC (39-68ºF) for 30 days in PVC bag
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            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

            From:

            To:

            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

            From:

            To:

            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.

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