Today's med: Phenytoin (FEN i toyn)
(brand names: Dilantin-125®, Dilantin®, Phenytek®)
Pharmacologic category: Anticonvulsant, Hydantoin
Other Drugs in this class:
Ethosuximide, Phenytoin sodium, Zonisamide, Vigabatrin, Tiagabine,Felbamate, Gabapentin enacarbil,Mesuximide, Ethotoin, Fosphenytoin sodium, Tiagabine hydrochloride,Divalproex sodium
Indications:
MOA: Stabilizes neuronal membranes and decreases seizure activity by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses; prolongs effective refractory period and suppresses ventricular pacemaker automaticity, shortens action potential in the heart.
Contraindications: Hypersensitivity to phenytoin, other hydantoins, or any component of the formulation; concurrent use of delavirdine (due to loss of virologic response and possible resistance to delavirdine or other non-nucleoside reverse transcriptase inhibitors [NNRTIs]); I.V.: Sinus bradycardia, sinoatrial block, second- and third-degree heart block, Adams-Stokes syndrome.
**Pregnancy risk factor D: high risk during pregnancy or lactation.
Adverse Effects: Patient education: Discuss specific use of drug and side effects with patient as it relates to treatment. Patient may experience presyncope, fatigue, blurred vision, illogical thinking, dizziness, nausea, or constipation. Have patient report immediately to prescriber depression, imbalance, severe asthenia, significant skin irritation, stomatitis, discolored urine, jaundice, ecchymosis, bleeding, or rash. Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat).
Effects not related to plasma phenytoin concentrations: Hypertrichosis, gingival hypertrophy, thickening of facial features, carbohydrate intolerance, folic acid deficiency, peripheral neuropathy, vitamin D deficiency, osteomalacia, systemic lupus erythematosus
Concentration-related effects: Nystagmus, blurred vision, diplopia, ataxia, slurred speech, dizziness, drowsiness, lethargy, coma, rash, fever, nausea, vomiting, gum tenderness, confusion, mood changes, folic acid depletion, osteomalacia, hyperglycemia
Related to elevated concentrations:
>20 mcg/mL: Far lateral nystagmus
>30 mcg/mL: 45° lateral gaze nystagmus and ataxia
>40 mcg/mL: Decreased mentation
>100 mcg/mL: Death
Cardiovascular: Bradycardia, cardiac arrhythmia, cardiovascular collapse, hypotension
Central nervous system: Dizziness, drowsiness, headache, insomnia, psychiatric changes, slurred speech
Dermatologic: Rash
Gastrointestinal: Constipation, gingival hyperplasia, enlargement of lips, nausea, taste disturbance, vomiting
Genitourinary: Peyronie’s disease
Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, thrombocytopenia
Hepatic: Hepatitis
Local: I.V. administration: Inflammation, irritation, necrosis, sloughing, tenderness, thrombophlebitis
Neuromuscular & skeletal: Paresthesia, peripheral neuropathy, tremor
Ocular: Blurred vision, diplopia, nystagmus
Rarely seen effects: Anaphylaxis, blood dyscrasias, coarsening of facial features, DRESS, dyskinesias, hepatitis, Hodgkin lymphoma,, hypertrichosis, immunoglobulin abnormalities, lymphadenopathy, lymphoma, macrocytosis, megaloblastic anemia, periarteritis nodosa, pseudolymphoma, SLE-like syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, venous irritation and pain
Standard Dosing:
Note: Phenytoin base (eg, oral suspension, chewable tablets) contains ~8% more drug than phenytoin sodium (~92 mg base is equivalent to 100 mg phenytoin sodium). Dosage adjustments and closer serum monitoring may be necessary when switching dosage forms.
Status epilepticus: I.V.:
Infants and Children: Loading dose: 15-20 mg/kg, then begin maintenance therapy usually 12 hours after loading dose
Adolescents and Adults: Loading dose: Manufacturer recommends 10-15 mg/kg; however, 15-20 mg/kg at a maximum rate of 50 mg/minute is generally recommended (Kalvianines, 2007; Lowenstein, 2005); initial maintenance dose: I.V. or Oral: 100 mg every 6-8 hours
Anticonvulsant (nonemergent use): Oral:
Loading dose: Children, Adolescents, and Adults: 15-20 mg/kg; consider prior phenytoin serum concentrations and/or recent dosing history if available; administer oral loading dose in 3 divided doses given every 2-4 hours to decrease GI adverse effects and to ensure complete oral absorption
Maintenance dose:
Infants and Children: Initial maintenance dose: 5 mg/kg/day in 2-3 divided doses; usual maintenance dose range: 4-8 mg/kg/day; maximum daily dose: 300 mg. Some experts suggest higher maintenance doses may be necessary in infant and young children (range: 7-9 mg/kg/day in divided doses).
Adolescents and Adults: Initial maintenance dose: 300 mg daily in 3 divided doses; may also administer in 1-2 divided doses using extended release formulation; adjust dosage based on individual requirements; usual maintenance dose range: 300-600 mg daily
Dosage adjustment in obesity: Adults: Loading dose: Use adjusted body weight (ABW) correction based on a pharmacokinetic study of phenytoin loading doses in obese patients (Abernethy, 1985). The larger correction factor (ie, 1.33) is due to a doubling of Vd estimated in these obese patients.
ABW = [(Actual body weight – IBW) x 1.33] + IBW
Maintenance doses should be based on ideal body weight, conventional daily doses with adjustments based upon therapeutic drug monitoring and clinical effectiveness. (Abernethy, 1985; Erstad, 2002; Erstad, 2004)
Oral: Suspension: Shake well prior to use. Absorption is impaired when phenytoin suspension is given concurrently to patients who are receiving continuous nasogastric feedings. A method to resolve this interaction is to divide the daily dose of phenytoin and withhold the administration of nutritional supplements for 1-2 hours before and after each phenytoin dose.
I.M.: Avoid this route (manufacturer recommends I.M. administration) due to severe risk of local tissue destruction and necrosis; use fosphenytoin if I.M. administration necessary (Boucher, 1996; Meek, 1999).
I.V.: Vesicant. Fosphenytoin may be considered for loading in patients who are in status epilepticus, hemodynamically unstable, or develop hypotension/bradycardia with I.V. administration of phenytoin. Although, phenytoin may be administered by direct I.V. injection, it is preferable that phenytoin be administered via infusion pump either undiluted or diluted in normal saline as an I.V. piggyback (IVPB) to prevent exceeding the maximum infusion rate (monitor closely for extravasation during infusion). The maximum rate of I.V. administration is 50 mg/minute in adults. Highly sensitive patients (eg, elderly, patients with pre-existing cardiovascular conditions) should receive phenytoin more slowly (eg, 20 mg/minute) (Meek, 1999). In neonates, the manufacturer recommends a maximum rate of 1-3 mg/kg/minute; however, a lower maximum rate of 0.5-1 mg/kg/minute is used clinically (Sankar, 2010; Shields, 1989). An in-line 0.22-5 micron filter is recommended for IVPB solutions due to the high potential for precipitation of the solution. Avoid extravasation. Following I.V. administration, NS should be injected through the same needle or I.V. catheter to prevent irritation.
pH: 10.0-12.3
SubQ: SubQ administration is not recommended because of the possibility of local tissue damage (due to high pH).
Folic acid: Phenytoin may decrease mucosal uptake of folic acid; to avoid folic acid deficiency and megaloblastic anemia, some clinicians recommend giving patients on anticonvulsants prophylactic doses of folic acid and cyanocobalamin. Folic acid 0.5 mg/day has been shown to reduce the incidence of phenytoin-induced gingival overgrowth in children (Arya, 2011). However, folate supplementation may increase seizures in some patients (dose dependent). Discuss with healthcare provider prior to using any supplements.
Calcium: Hypocalcemia has been reported in patients taking prolonged high-dose therapy with an anticonvulsant. Some clinicians have given an additional 4000 units/week of vitamin D (especially in those receiving poor nutrition and getting no sun exposure) to prevent hypocalcemia.
Vitamin D: Phenytoin interferes with vitamin D metabolism and osteomalacia may result; may need to supplement with vitamin D
Tube feedings: Tube feedings decrease phenytoin absorption. To avoid decreased serum levels with continuous NG feeds, hold feedings for 1-2 hours prior to and 1-2 hours after phenytoin administration, if possible. There is a variety of opinions on how to administer phenytoin with enteral feedings. Be consistent throughout therapy.
Injection may contain sodium.
Warnings: Phenytoin must be administered slowly. Intravenous administration should not exceed 50 mg/minute in adult patients. In pediatric patients, intravenous administration rate should not exceed 1-3 mg/kg/minute or 50 mg/minute whichever is slower.
Drug
interactions: LINK: http://www.drugs.com/drug-interactions/phenytoin.html
- 47 major drug interactions (113 brand and generic names)
- 934 moderate drug interactions (5716 brand and generic names)
- 67 minor drug interactions (355 brand and generic names)
Amphetamines: May decrease the serum concentration of Phenytoin. Monitor therapy
Benzodiazepines: May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam. Monitor therapy
Phenytoin keeps seizures from goin'.....
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