When giving intravenous IV phenytoin Which of the following methods should you use?

• Uses
  • What Is Phenytoin and How Does It Work?
• Dosage
  • What Are Dosages of Phenytoin?
• Side Effects
  • What Are Side Effects Associated with Using Phenytoin?
• Drug Interactions
  • What Other Drugs Interact with Phenytoin?
• Warnings and Precautions
  • What Are Warnings and Precautions for Phenytoin?

What Is Phenytoin and How Does It Work?

Phenytoin is used to prevent and control seizures [also called an anticonvulsant or antiepileptic drug]. It works by reducing the spread of seizure activity in the brain.

• Phenytoin may also be used to treat certain types of irregular heartbeats.
• Phenytoin is available under the following different brand names: Dilantin, Dilantin 125, and Phenytek.

What Are Dosages of Phenytoin?

Dosages of Phenytoin:

Dosage Forms and Strengths

Capsule, immediate-release

• 30 mg
• 100 mg

Capsule, extended-release

• 100 mg
• 200 mg
• 300 mg

Tablet, chewable

• 50 mg

Oral suspension

• 125 mg/5mL

Injectable solution

• 50 mg/mL

Dosage Considerations – Should be Given as Follows:

Seizures

Status epilepticus

• Adult: Load 10-15 mg/kg or 15-20 mg/kg at 25-50 mg/min, THEN
• Maintenance: 100 mg intravenously/orally every 6-8 hours as needed
• Administer intravenous [IV] slowly; not to exceed 50 mg/minutes
• Pediatric: 15-20 mg/kg intravenously [IV] in single or divided dose; if necessary may administer additional dose of 5-10 mg/kg 10 minutes after loading dose
• Maintenance: 4-8 mg/kg/day IV divided twice daily

Anticonvulsant, Adult

Tablet

• 100 mg orally three times daily
• 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 orally three times daily, 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-hour intervals; initiate dosage 24 hours after loading dose
• Loading dose not for administration to patients with a history of the renal or hepatic disease; reserve for patients who require rapid steady serum levels, when IV administration is not desirable, and for patients in a clinic or hospital setting where phenytoin levels can be closely monitored
• Treatment [naive]: 100 mg orally three times daily initially
• May adjust dose no sooner than 7-10 day intervals
• Therapeutic range: 10-20 mcg/L [total] or 1-2 mcg/L free drug

Anticonvulsant, Children and Adolescents

Immediate release

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

Control of Tonic-Clonic and Complex Partial Seizures, Pediatric

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 [less than 28 days]

• Initial: 5-8 mg/kg/day intravenously [IV]/orally divided every 8-12 hours

Age-based maintenance dose

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

Dosing Considerations

• Children under 6 years: Potential toxic dose, 20 mg/kg
• Therapeutic range: 10-20 mcg/L [total] or 1-2 mcg/L free drug
• ALWAYS administer intravenous [IV] slowly; not to exceed 1-3 mg/kg/minute

QUESTION

What Other Drugs Interact with Phenytoin?

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Phenytoin has severe interactions with at least 28 different drugs.
• Phenytoin has serious interactions with at least 83 different drugs.
• Phenytoin has moderate interactions with at least 286 different drugs.
• Phenytoin has mild interactions with at least 121 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

What Are Warnings and Precautions for Phenytoin?

Warnings

Cardiovascular risk associated with rapid infusion rates:

• Risk of low blood pressure [hypotension] and irregular heartbeats [arrhythmias] with infusion rates that exceed 50 mg/minute in adults and 1-3 mg/kg/minute [or 50 mg/minute, whichever is lower] for pediatric patients
• Careful cardiac monitoring is needed during and after intravenous [IV] administration
• These events have also been reported at or below 50 mg/minute
• Reduce infusion rate or discontinuation may be needed

This medication contains phenytoin. Do not take Dilantin, Dilantin 125, or Phenytek if you are allergic to phenytoin or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• 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

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Phenytoin?”

Long-Term Effects

• Decreased bone mineral density reported with chronic use.
• See "What Are Side Effects Associated with Using Phenytoin?”

Cautions

• Erratically absorbed when administered intramuscularly [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/minute or 50 mg per minute, whichever is slower; although the 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.
• If early signs of dose-related central nervous system [CNS] toxicity develop, serum levels should be checked immediately.
• DRESS typically, although not exclusively, presents with fever, rash, enlarged lymph nodes [lymphadenopathy], and/or facial swelling, in association with other organ system involvement.
• Phenytoin induces hepatic metabolizing enzymes, which may enhance the metabolism of vitamin D and decreases 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 a fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or 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.
• 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.
• Risk of low blood pressure [hypotension] and irregular heartbeats [arrhythmias] with infusion rates that exceed 50 mg/minute in adults and 1-3 mg/kg/minute [or 50 mg/minute, whichever is lower] 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 oral contraceptive pills ineffective because of induction of hepatic metabolism.

Risk of gingival hyperplasia.

• If rash occurs including toxic epidermal necrolysis [TEN] and Stevens-Johnson syndrome [SJS reported; onset of symptoms is usually within 28 days, but can occur later; phenytoin should be discontinued at the first sign of a rash unless the rash is clearly not drug-related; if signs or symptoms suggest SJS/TEN, discontinue therapy permanently and consider alternative therapy; evaluate for signs and symptoms of DRESS, also known as multi-organ hypersensitivity.
• Local toxicity [purple glove syndrome] that includes edema, discoloration, and pain distal to the site of injection has been reported following peripheral intravenous [IV] injection; may or may not be associated with extravasation; this syndrome may not develop for several days after injection.
• Intravenous [IV] infusion is not recommended by many due to poor solubility and risk of crystal formation; others state it is doable with the right solvent and concentration.
• Good for automatic and reentrant arrhythmias, not paroxysmal supraventricular tachycardias [PSVTs].
• 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 non-depolarizing 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.
• High blood sugar [hyperglycemia], resulting from the drug's inhibitory effect on insulin release reported; phenytoin may also raise serum glucose level in patients with 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 are present, combined drug therapy is 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; a 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.

Pregnancy and Lactation

• 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 on the website //www.aedpregnancyregistry.org/.
• 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] was 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 one month before birth.
• Phenytoin is secreted in human milk; developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for therapy and any potential adverse effects on breastfed infants from phenytoin or the underlying maternal condition.

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