dilantin
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Synonyms
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Phenytoin, known widely by its brand name Dilantin, is one of those foundational antiepileptic drugs that every neurologist and emergency physician has a deep, almost personal, relationship with. It’s a hydantoin derivative, a sodium channel blocker that’s been stabilizing neuronal membranes and preventing the spread of seizure activity since the 1930s. We’re talking about a drug that’s saved countless lives, but it’s also one that demands respect due to its narrow therapeutic index and complex pharmacokinetics. I remember my first night on call as a resident, scrambling to load a status epilepticus patient with IV phenytoin, watching the cardiac monitor like a hawk for that dreaded hypotension or bradycardia. It’s not just a medication; it’s a rite of passage.
Key Components and Bioavailability of Dilantin
The active pharmaceutical ingredient is phenytoin itself, available in several salt forms to tweak solubility and absorption—phenytoin sodium being the most common for oral and intravenous use. There’s also the prodrug fosphenytoin, which is a phosphate ester prodrug that converts to phenytoin in the blood. Fosphenytoin is a game-changer for IV administration because it’s water-soluble, unlike phenytoin which requires a propylene glycol and ethanol vehicle that can cause all sorts of infusion site reactions and cardiovascular instability if pushed too fast. Bioavailability for oral phenytoin is pretty high, around 90% for the capsule forms, but it’s notoriously variable due to its saturation kinetics. You hit a point where small dose increases can lead to massive jumps in serum levels—that’s why we’re always checking levels and counseling patients on consistency with meals, since it’s better absorbed with food. The extended-release formulations help smooth out some of those peaks and troughs, but they’re not perfect. We had a patient, Mrs. Gable, 68, who was switched from generic immediate-release to Dilantin brand extended-release, and her levels went from subtherapeutic to toxic within a week because nobody adjusted for the different release profiles. It’s these nuances that separate adequate care from excellent management.
Mechanism of Action of Dilantin: Scientific Substantiation
At its core, phenytoin works by blocking voltage-gated sodium channels in their inactivated state. This stabilizes neuronal membranes and prevents the high-frequency repetitive firing that characterizes seizure activity. It’s use-dependent, meaning it preferentially binds to channels that are firing a lot, which is why it’s so effective in seizures without completely shutting down normal neuronal function. But it’s not selective—it affects peripheral nerves, cardiac tissue, you name it. That’s where the side effect profile comes from. There’s also some evidence it modulates calcium channels and inhibits glutamate release, but the sodium channel blockade is the star of the show. I recall a journal club debate back in fellowship where we tore apart a paper suggesting phenytoin had significant effects on GABAergic transmission—turned out the in vitro concentrations were nowhere near clinically achievable. It’s a reminder to always cross-check mechanistic studies with pharmacokinetic reality.
Indications for Use: What is Dilantin Effective For?
Dilantin for Tonic-Clonic Seizures
It’s a first-line agent for generalized tonic-clonic seizures and focal seizures with impaired awareness. The evidence base is decades deep, with randomized trials and real-world data supporting its efficacy. We had a construction worker, Marco, 42, whose tonic-clonics were uncontrolled on levetiracetam due to non-adherence from behavioral side effects. Switched him to phenytoin with strict level monitoring, and he’s been seizure-free for 3 years now, back operating heavy machinery with a commercial driver’s license clearance.
Dilantin for Status Epilepticus
IV phenytoin or fosphenytoin is a standard second-line agent after benzodiazepines in convulsive status. The loading dose math is critical—20 mg/kg PE (phenytoin equivalents) for fosphenytoin, but you have to adjust for obesity, hypoalbuminemia, renal function. I once saw a junior resident order a standard load on a patient with cirrhosis and low albumin, not realizing the free fraction was through the roof—patient became ataxic and lethargic for days. It’s these pharmacokinetic landmines that keep you humble.
Dilantin for Post-Traumatic Seizure Prophylaxis
This is a bit more controversial. The evidence for preventing late post-traumatic seizures is weak, but it’s still used in some neurotrauma protocols for early seizure prevention, especially in penetrating brain injury. The neurosurgeons and neurologists at my institution have gone back and forth on this—some swear by it for the first week, others think it’s outdated. We had a young soldier, Derek, 24, with a shrapnel injury to the temporal lobe, who was on phenytoin prophylaxis. He never had a seizure, but we’ll never know if it was the drug or just his individual course.
Off-Label Uses: Neuropathic Pain and Arrhythmias
There’s historical use for trigeminal neuralgia and other neuropathic pain syndromes, though it’s largely supplanted by anticonvulsants like carbamazepine and gabapentinoids. In cardiology, it’s occasionally used for digitalis-induced arrhythmias due to its effects on cardiac sodium channels. Not something you see often, but it’s in the toolbox.
Instructions for Use: Dosage and Course of Administration
Dosing is highly individualized. For adults starting oral therapy, we often begin with 300 mg/day in divided doses or once daily if using extended-release, then titrate based on response and levels. The therapeutic range is 10-20 mcg/mL total, but I always look at free phenytoin levels if there’s renal impairment, hypoalbuminemia, or pregnancy—aim for 1-2 mcg/mL free. Loading doses for acute control: oral 15-20 mg/kg in divided doses, or IV 20 mg/kg PE for fosphenytoin. Here’s a quick reference table for maintenance dosing in adults:
| Indication | Initial Daily Dose | Titration | Target Level | Notes |
|---|---|---|---|---|
| New-Onset Seizures | 300 mg | Increase by 30 mg every 1-2 weeks | 10-20 mcg/mL | With meals for consistency |
| Status Epilepticus | 20 mg/kg IV PE | None | 15-25 mcg/mL | Monitor ECG and BP during infusion |
| Prophylaxis | 300 mg | As tolerated | 10-20 mcg/mL | Short-term use preferred |
Pediatric dosing is weight-based, usually 5 mg/kg/day divided BID, but it varies. Always check levels at steady state, which takes 7-10 days after a dose change.
Contraindications and Drug Interactions with Dilantin
Absolute contraindications include hypersensitivity to phenytoin or other hydantoins, sinus bradycardia, SA block, 2nd/3rd degree AV block, Adams-Stokes syndrome. Relative contraindications: hepatic impairment, porphyria. The drug interaction profile is a nightmare—it’s a potent inducer of CYP2C9, CYP2C19, and CYP3A4, so it speeds up the metabolism of oral contraceptives, warfarin, many antidepressants, and even other antiepileptics like carbamazepine. Conversely, drugs that inhibit these enzymes (like fluoxetine, amiodarone, isoniazid) can skyrocket phenytoin levels. I had a clinic patient, Linda, 57, stable on phenytoin for years, who started fluconazole for a recurrent fungal infection—her phenytoin level shot up to 38, presented with nystagmus and ataxia. We held doses for 2 days, restarted at a lower dose, and she was fine, but it’s a classic example of why medication reconciliation isn’t just bureaucratic paperwork.
Clinical Studies and Evidence Base for Dilantin
The Veterans Affairs cooperative studies in the 1980s and 1990s cemented phenytoin’s role in partial and generalized tonic-clonic seizures, showing comparable efficacy to carbamazepine and phenobarbital. More recent studies, like the SANAD trial, have favored newer agents like lamotrigine and levetiracetam for focal seizures due to better tolerability, but phenytoin remains a workhorse in resource-limited settings and acute care. For status epilepticus, the landmark studies (like the Veterans Affairs Status Epilepticus Cooperative Study) established lorazepam followed by phenytoin as superior to phenobarbital or diazepam-phenytoin combinations. A 2012 meta-analysis in Epilepsia reaffirmed its efficacy but highlighted the safety advantages of fosphenytoin. The evidence for neuroprotection or prophylactic use is shakier—a Cochrane review found no benefit for long-term seizure prevention after traumatic brain injury, which has shifted practice in many centers.
Comparing Dilantin with Similar Products and Choosing a Quality Product
Versus levetiracetam: Phenytoin has more drug interactions and non-linear kinetics, but levetiracetam can cause psychiatric side effects. Versus carbamazepine: Both are enzyme inducers, but carbamazepine has more autoimmune risks and requires slow titration. Versus valproate: Phenytoin doesn’t have the weight gain or tremor issues, but valproate is broader spectrum for generalized seizures. Brand vs. generic: The FDA considers them equivalent, but some patients do report differences in control due to slight variations in absorption—if a patient is stable on a particular manufacturer, I try not to switch. For IV use, fosphenytoin is objectively safer and better tolerated than phenytoin, though more expensive.
Frequently Asked Questions (FAQ) about Dilantin
What is the recommended course of Dilantin to achieve results?
It’s chronic therapy for epilepsy—lifelong in many cases. You’ll see seizure reduction within days to weeks after reaching therapeutic levels, but it’s not a cure.
Can Dilantin be combined with other seizure medications?
Yes, it’s often used in polytherapy, but beware of interactions—especially with valproate, which displaces phenytoin from protein binding sites and inhibits its metabolism.
Is Dilantin safe during pregnancy?
Pregnancy Category D—it’s associated with fetal hydantoin syndrome and major malformations. We try to avoid or minimize use in pregnancy, but sometimes it’s the only effective option. Free level monitoring is essential due to physiological changes.
What are the signs of Dilantin toxicity?
Nystagmus, ataxia, slurred speech, lethargy, confusion. Severe overdose can cause coma, hypotension, bradycardia.
How should I monitor while on Dilantin?
Regular serum levels (trough), LFTs, CBC, vitamin D and bone density monitoring long-term due to osteomalacia risk.
Conclusion: Validity of Dilantin Use in Clinical Practice
Despite the arrival of newer antiepileptics, phenytoin retains a vital role in acute seizure management and for certain patients with focal or generalized tonic-clonic seizures. Its benefits in rapid control and low cost are balanced by a narrow therapeutic window, complex pharmacokinetics, and significant interaction potential. For carefully selected patients with appropriate monitoring, it remains a valuable tool in the epileptologist’s arsenal.
I’ll never forget a long-term follow-up with a patient, Mr. Henderson, who’d been on phenytoin since the 1970s for post-traumatic epilepsy after a motorcycle accident. He’d developed gingival hyperplasia, mild peripheral neuropathy, and osteopenia over the decades, but he’d also raised a family, run a small business, and never had a breakthrough seizure. At his last visit, he told me, “This drug gave me my life back, even with the side effects.” It’s a reminder that our decisions are never just about molecules and mechanisms—they’re about real people and their stories. We recently transitioned him to levetiracetam due to his age and bone health concerns, and he’s doing well, but that longitudinal relationship with a medication is something you don’t see in the trials. It’s the art behind the science.