#dilantin

Lots of religious days of importance are happening this week - including the start of Holy Week for Christians coinciding with Jewish Passover celebrations. As my mother died on Easter Sunday, it's been a conflicting time for me for many years. Twenty-seven years ago this week, my family was everywhere emotionally. We'd received the devastating news a few weeks before that my mom's breast cancer had metastasized to not only her lungs and liver (which she knew about), but also to her brain. In addition to the struggle that comes with knowing someone you love has only a short time left in this physical plain, my dad insisted that my mom not be told about the new diagnosis, and my disagreement with his insistence led to a lot of additional tension. Hospice was around, as was a day nurse that helped administer medications to mom during the day. Back then, adjuvant treatment included oral dilantin to help eliminate brain swelling. It had to be administered every six or eight hours, if I recall - plus an N-G tube had to be taken care of to make sure liquid nutrients could be given as well, as she was unable to eat. Add the steady stream of family and friends happening by to visit, and it's not hard to get that there was lots of movement in and around the house during Holy Week that year. But the push to aim for normalcy was strong. I'd moved back home less than a year before from Philadelphia to deal with a career change/transition from photojournalism that involved deciding if graduate school was the direction to take. In between gathering GRE and grad program application information, I was also training for an outside chance at trying for another Olympic team. Yes, things were crazy busy. Because mom was pretty immobile, changing her bed sheets was done the same way hospitals do it: by rolling her over instead of getting her out of bed. But a new Hospice bed delivery required that we get her up to actually change beds. During the relatively quick exchange, we helped her sit in the big comfy chair in the room, a plush recliner that happened to sit near a dresser. Not two minutes after she got into the chair, she glanced into the mirror and was pretty shocked to see that all of her hair was gone from the radiation she'd received in the hospital when her metastasis was discovered. "Wow," she said as she rubbed her head. "I'm as bald as a cue ball!" She didn't ask where her hair had gone or why, but I think she knew. As the Olympic Trials were around the corner, I had decided to open my outdoor track season with a meet in New Jersey that seemed to be about an hour or so away. My mom was always my biggest cheerleader, traveling the country with me to meets through the years - both during and after college. She was actually more excited about the meet than I was. The night before the meet was Good Friday. As lots of folks called to see how she was, I remember overhearing my dad telling folks he hadn't seen in years that my mom was acting a bit delirious, describing her as "talking out of her head." That totally shocked me, because I hadn't witnessed anything like that at all. She and I talked all the time, although she talked a lot less than she use to. I remember giving her a manicure that night. While I painted, she talked a bit about the meet, asking if my uniform was clean and if my car was gassed up and ready to go. She said she wished she could go and watch me compete. While I painted my own nails the same color I told her she'd be with me in spirit, but she was already fast asleep. I took a picture of our hands together a few minutes later.

Common Brand Names: Dilantin

Therapeutic Class: A hydantoin-derivative anticonvulsant structurally related to the barbiturates.

Common Injectable Dosage Forms:

Injection: 50 mg/mL in vials and syringes (46 mg phenytoin)

Dosage Ranges:

To achieve therapeutic serum concentrations (10-20 µg/mL) within 1-2 hours for status epilepticus, a dose of 10-15 mg/kg may be given at a rate not exceeding 50 mg/minute. In children, give 250 mg/m2. Most clinicians recommend doses of 15-18 mg/kg at a rate of 25-50 mg/minute and children may receive 10-15 mg/kg at a rate of 0.5-1.5 mg/kg/minute to a maximum of 20 mg/kg in 24 hours. Maintenance therapy is generally instituted at 100 mg every 8 hours, with dosages titrated individually until desired response is obtained. Patients should be converted to oral therapy as soon as feasible.

For glycoside-induced arrhythmias, 100 mg IV has been given at 5-minute intervals until normal rhythm resumes or until a maximum of 1 gram is reached.

Therapeutic Drug Level: Between 10-20 µg/mL

Administration and Stability: Direct IV injection in a large vein of undiluted solution (50 mg/mL) is recommended at a rate not to exceed 50 mg/minute. Although dilution for IV infusion is generally not recommended, it has been used by diluting with a compatible solution (NS) to a concentration less than 6.7 mg/mL and infusing immediately while observing carefully for precipitation. Use of in-line 0.22-5-micron filter recommended for IVPB solutions due to high potential for precipitate to form. IM administration has been used when other routes are unavailable, but, since absorption is erratic, is not generally recommended and has been specifically limited to 1 week of therapy. Stable for 14 hours at room temperature when diluted to 2 mg/mL with NS. pH 10-12.3

Pharmacology/Pharmacokinetics: Phenytoin limits seizure activity by reducing the post-tetanic potentiation of synaptic transmission. This is accompanied by reducing the passive influx of sodium ions or increasing sodium pump activity to eliminate accumulation of sodium ions during tetanic stimulation. Therapeutic plasma concentrations are obtained in 1-2 hours following the administration of an IV loading dose, with steady state therapeutic levels of 7.5-20 mcg/mL achieved within 7-10 days in the absence of a loading dose. Phenytoin is highly protein bound (95%) with a plasma half-life of approximately 22 hours. Phenytoin is metabolized in the liver by a saturable process to inactive metabolites and excreted in the urine (unchanged drug 2-5%).

Drug and Lab Interactions: Since phenytoin is highly protein bound and metabolized in the liver, drugs which possess either of these qualities may interact with this drug. Drugs which increase phenytoin levels by inhibition of metabolism include sulfonamides, phenylbutazone, PHENOTHIAZINES, isoniazid, WARFARIN, and benzodiazepines. PHENOBARBITAL and CARBAMAZEPINE may decrease phenytoin levels by induction of the hepatic enzyme system. Phenytoin may increase the levels of such drugs as thyroid supplements and methotrexate by competitive protein binding. Tricyclic antidepressants may increase chance of seizures and oral contraceptives may increase plasma levels of phenytoin be decreasing hepatic metabolism and/or decreasing protein binding.

Contraindications/Precautions: Contraindicated in patients with known hypersensitivity to other hydantoin agents, sinus bradycardia, sinoatrial block, second- or third-degree atrioventricular block, or Adams-Strokes syndrome. Should be used with caution in pregnant patients and levels monitored frequently due to altered metabolism, and also in patients with respiratory depression, MI, CHF, or otherwise damaged myocardium. Antiepileptic drugs should not be abruptly discontinued because of the possibility of increased seizure frequency. If hypersensitivity occurs, rapid substitution of an alternative therapy may be required. Use with caution in patients with impaired hepatic function. Stop use if rash develops. Pregnancy Category D.

Monitoring Parameters: BP, vitals, plasma phenytoin level, CBC, LFTs

Adverse Effects: Adverse effects are varied, frequent, and may occasionally be serious in nature. More serious effects include exfoliative dermatitis, Stevens-Johnson syndrome, lymphadenopathy, blood dyscrasias, and CNS toxicity related to high serum levels. Other effects reported include hirsutism, gingival hyperplasia, thrombophlebitis, tissue necrosis at injection sites, osteomalacia, and GI effects.

Brand Name: Dilantin, Kapseals

Generic Available

Common Dosage Forms*:

Capsules, extended release: 30 mg, 100 mg

*Phenytoin is also available in immediate release and injectable formulations

FDA Indications/Dosages:

For the control of tonic-clonic and psychomotor seizures and prevention and treatment of seizures occurring during or following neurosurgery:

Adult Divided Dose Therapy: 100 mg three times a day to start then adjust to individual patient response. Once controlled with TID dosing, patient may be switched to once-a-day dosing using the same total dose (I.e., 100 mg TID to 300 mg once daily).

Adult Loading Dose: Give a 400 mg, a 300 mg, and another 300 mg dose at two-hour intervals. Then begin normal maintenance dosage 24 hours following loading dose.

Pediatric Initial Dose: 5 mg/kg/day in 2-3 equally divided doses, may increase up to 300 mg/day.

Pediatric Maintenance Dose: 5 mg/kg/day, children over 6 years old may require up to 300 mg/day.

*Also available as Dilantin Infatabs, Dilantin-30 Pediatric Suspension, Dilantin-125 Suspension, and Dilantin injection (all non-extended-release forms of phenytoin). See manufacturer’s recommended indications and dosage ranges for these products.

Monitor: Serum phenytoin, LFT, CBC

Pharmacology/Pharmacokinetics: Phenytoin increases the extrusion of sodium ions from neurons and cardiac myocytes. This produces a stabilization of the excitability to repetitive stimuli.The primary site of action appears to be the motor cortex. Plasma half-life averages 22 hours. Steady state levels are reached in 7-10 days. Peak serum levels are reached in 6-12 hours. Therapeutic serum levels are between 10-20 mcg/mL. Phenytoin is highly protein bound, metabolized in the liver, and excreted in the urine.

Drug Interactions: AMIODARONE, CHLORAMPHENICOL, CIMETIDINE, DISULFIRAM, ISONIAZID, ORAL ANTICOAGULANTS, phenacemide, phenylbutazone, SULFONAMIDES, FLUCONAZOLE, or TRIMETHOPRIM may increase serum levels. ANTINEOPLASTICS may decrease actions. May decrease CARBAMAZEPINE serum levels. Diazoxide, folic acid, RIFAMPIN, SUCRALFATE, and theophylline may decrease serum levels. Valproic acid may increase actions. Hepatotoxicity may be increased when used with acetaminophen. May increase metabolism of corticosteroids, DISOPYRAMIDE, doxycycline, metyrapone, mexiletine, quinidine, and THEOPHYLLINES. May decrease actions of cyclosporine, levodopa, ORAL CONTRACEPTIVES, and nondepolarizing muscle relaxants. May increase serum levels of primidone. Serious hypotension may occur when given during a dopamine infusion.

Contraindications/Precautions: Use is contraindicated in patients hypersensitive to phenytoin or other hydantoins. Use with caution in pregnant women, in patients with impaired liver function, and in diabetic patients. Discontinue use if rash develops. Pregnancy Category D.

Adverse Effects: Nystagmus, ATAXIA, SLURRED SPEECH, MENTAL CONFUSION, nausea, vomiting, RASH, hirsutism, gingival hyperplasia, constipation, dizziness, and drowsiness.

Patient Consultation:

Take with food to enhance absorption and to reduce GI upset.

May cause drowsiness. Use caution while operating machinery or when mental alertness is required.

Call your physician if a skin rash develops.

Consult a physician or pharmacist before using any nonprescription medications or alcohol.

Practice good oral hygiene to help prevent gingival hyperplasia.

Diabetic patients should monitor blood glucose levels closely while taking this medication.

Do not discontinue therapy without first consulting a physician.

Store in a cool, dry place away from sunlight and children.