Dilantin Side Effects

Generic Name: phenytoin

Note: This page contains information about the side effects of phenytoin. Some of the dosage forms included on this document may not apply to the brand name Dilantin.

Not all side effects for Dilantin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to phenytoin: oral capsule, oral capsule extended release, oral suspension, oral tablet chewable

Other dosage forms:

In addition to its needed effects, some unwanted effects may be caused by phenytoin (the active ingredient contained in Dilantin). In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking phenytoin:

More common
  • Decreased coordination
  • mental confusion
  • nervousness
  • slurred speech
  • trouble with breathing, speaking, or swallowing
  • unsteadiness, trembling, or other problems with muscle control or coordination
  • Inability to move the eyes
  • increased blinking or spasms of the eyelid
  • shakiness and unsteady walk shakiness in the legs, arms, hands, or feet
  • sticking out of the tongue
  • trembling or shaking of the hands or feet
  • twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
  • uncontrolled twisting movements of the neck, trunk, arms, or legs
  • unusual facial expressions
Incidence not known
  • Abdominal or stomach pain
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • blisters, hives, or itching
  • bloating of the abdomen or stomach
  • blood in the urine or stools
  • bloody, black, or tarry stools
  • chest pain
  • chills
  • cough or hoarseness
  • dark urine
  • diarrhea
  • difficulty with moving
  • fainting spells
  • fever with or without chills
  • general feeling of discomfort or illness
  • general feeling of tiredness or weakness
  • hair loss
  • headache
  • high fever
  • irregular heartbeat
  • irritation in the mouth
  • joint or muscle pain
  • light-colored stools
  • lower back or side pain
  • muscle stiffness
  • nausea or vomiting
  • numbness, tingling, or pain in the hands or feet
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • redness and swelling of the gums
  • skin blisters
  • skin rash
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swollen, painful, or tender lymph glands in the neck, armpit, or groin
  • unusual bleeding or bruising
  • unusual tiredness
  • upper right abdominal or stomach pain
  • weakness
  • weight loss
  • yellow eyes or skin

Some of the side effects that can occur with phenytoin may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Trouble sleeping
  • uncontrolled eye movements
Incidence not known
  • Difficulty having a bowel movement (stool)
  • enlarged lips
  • feeling of constant movement of self or surroundings
  • increased hair growth on the forehead, back, arms, or legs
  • pain of the penis on erection
  • sensation of spinning

For Healthcare Professionals

Applies to phenytoin: compounding powder, injectable solution, oral capsule, oral capsule extended release, oral suspension, oral tablet chewable

Nervous system

Chronic administration may result in memory impairment, intellectual decline, and irritability. These effects are frequently subtle. Psychiatric illness (including mania and psychosis), headaches, dyskinesias (including chorea, dystonia, and tremor), benign intracranial hypertension, opsoclonus, ophthalmoplegia, sensory polyneuropathy, cerebellar degeneration, myoclonus, parkinsonism, and asterixis have also been reported less frequently.

The pathologic characteristics of phenytoin-induced neuropathy include axonal shrinkage and secondary demyelination.

At very high plasma levels, phenytoin (the active ingredient contained in Dilantin) may rarely precipitate seizures and/or status epilepticus.

Nervous system effects are common and frequently dose-dependent. Nystagmus, ataxia, slurred speech, impaired cognition, and diplopia frequently occur. At higher plasma levels, drowsiness, lethargy, and coma may occur.
Postmarketing reports: Vertigo


Abrupt discontinuation in epileptic patients may precipitate worsening of seizures and status epilepticus. Additionally, phenytoin (the active ingredient contained in Dilantin) may exacerbate preexisting lupus.

Other side effects have included tibial and facial edema, altered taste, coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.


Local side effects have included edema, discoloration, and pain of the distal limb (described as "purple glove syndrome") following peripheral IV phenytoin (the active ingredient contained in Dilantin) injection. This may or may not be associated with extravasation. Although resolution of symptoms may be spontaneous, skin necrosis and limb ischemia have occurred and required such interventions as fasciotomies, skin grafting and amputation.


Cardiovascular side effects include hypotension, bradycardia, other arrhythmias and cardiac arrest rarely. These complications are most likely to occur in patients receiving parenteral phenytoin (the active ingredient contained in Dilantin) or in patients with underlying cardiovascular disease.

Phenytoin has been implicated as a possible cause of myocarditis related to drug hypersensitivity.


Hypersensitivity side effects have been reported. Phenytoin is the most common cause of the anticonvulsant hypersensitivity syndrome. A variety of hypersensitivity reactions have been reported in association with phenytoin (the active ingredient contained in Dilantin) use. Reactions frequently involve generalized rashes, eosinophilia, fever, lymphadenopathy, and hepatic derangements. Myopathy, rhabdomyolysis, renal dysfunction, disseminated intravascular coagulation, and purpura fulminans have also been reported to occur as part of a phenytoin hypersensitivity reaction.

The constellation of findings which includes lymphadenopathy, fever, exfoliative dermatitis, eosinophilia and hepatic damage is often called "pseudolymphoma" and may be fatal.

One study has suggested that hypersensitivity to phenytoin may occur in a familial pattern.


The more serious hepatic effects have often been reported in association with hypersensitivity reactions.

Hepatic side effects including elevated liver function tests, acute hepatitis, chronic persistent hepatitis, cholestasis and fulminant hepatic failure have all been reported. Mild enzyme elevation is common and often represents enzyme induction and not hepatic pathology.


Dermatologic side effects including Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus vulgaris, erythema multiforme, a pseudonymous fungoides syndrome, erythroderma, facial pustules, hyperpigmentation, coarsening of facial features, hirsutism, hypertrichosis (which is occasionally irreversible), and lupus-like symptoms have been reported. A case of acquired acromelanosis has been reported. Another case report has suggested that phenytoin (the active ingredient contained in Dilantin) may cause an erythematous lichenified rash of the lips.

One study of the occurrence of subacute local cutaneous reactions in patients receiving IV phenytoin reported that 29 out of 115 patients (25.2%) had such reactions. These included 22 mild reactions and 7 moderate reactions.

Erythema multiforme is more likely if the patient is receiving concomitant X-ray therapy.


Respiratory side effects including life-threatening respiratory depression may occur, particularly during acute intoxication or following rapid intravenous dosing, especially with concomitant administration of benzodiazepines and barbiturates.

Cases of an acute pulmonary disease (which may be part of a hypersensitivity angiitis) have been reported following treatment with phenytoin. Pathologically, the disease has been described both as an interstitial pneumonitis and as a lymphocytic interstitial pneumonia.


Oncologic side effects have included cases of increased frequency of malignancy (particularly Hodgkin's and non-Hodgkin's lymphoma and lung cancer) in patients taking phenytoin (the active ingredient contained in Dilantin) and other antiepileptic medications. Other investigators have not found an association with malignancy.


A reversible IgA deficiency has been reported. Several case reports have suggested that phenytoin (the active ingredient contained in Dilantin) may rarely induce panhypogammaglobulinemia. Another case report has suggested that phenytoin may cause a permanent deficiency in B cell immunity.

Other case reports suggest that phenytoin may cause bone marrow granulomata formation.

Hematologic side effects including bone marrow suppression, agranulocytosis, thrombocytopenia, pure red cell aplasia, and prothrombin deficiency have been reported rarely.


One report has suggested that phenytoin (the active ingredient contained in Dilantin) therapy may be associated with the development of sarcoidosis. However, a clear relationship between sarcoidosis and phenytoin therapy has not been established.

The systemic granulomatous vasculitis associated with phenytoin requires discontinuation of phenytoin and high-dose steroid therapy.

Immunologic side effects including a lupus-like syndrome associated with the presence of lupus anticoagulant may occur. Cases of a systemic granulomatous vasculitis and necrotizing angiitis have been reported.


Renal side effects including nephrotic syndrome and interstitial nephritis have been reported in association with phenytoin (the active ingredient contained in Dilantin) therapy.


Endocrine effects include glucose intolerance and decreases in serum T4 and FT4. Favorable changes in lipid profiles have also been reported and include elevated HDL cholesterol and lower LDL cholesterol. Increases in serum estradiol levels have been reported and may contribute to the sexual dysfunction which may occur in males treated with phenytoin (the active ingredient contained in Dilantin) Gynecomastia has also been reported. Alterations in vitamin D metabolism have been reported in patients taking phenytoin and other anticonvulsants. Hypocalcemia and osteomalacia have been reported.

Phenytoin increases the rate of T4 and T3 metabolism and may lead to hypothyroidism in patients with hypothyroidism who are being treated with T4. Phenytoin may also cause a 20% to 40% decrease in serum total and free T4 concentrations and a smaller decrease in serum total and free T3 concentrations in patients who have no thyroid disease.

Additionally, the presence of diabetes mellitus (both types I and II) has been associated with alterations in the pharmacokinetic disposition of phenytoin. Decreases in plasma protein binding, Vmax and Vmax/Km have been reported. (Km is the serum concentration at which 50% saturation occurs and Vmax is the maximum rate of metabolism.) As a result, lower steady-state concentration of phenytoin may occur in patients with diabetes mellitus.


Salivary gland hypertrophy has also been reported. A single case of drug-induced esophageal stricture has been reported.

Gastrointestinal side effects including gingival hyperplasia (in as many as 50% of treated patients) have been reported. The gingival hyperplasia associated with phenytoin is occasionally severe enough to merit surgical removal. Nausea, vomiting, and constipation have been reported.


Musculoskeletal side effects including myopathy in association with anticonvulsant osteomalacia has been reported in patients taking phenytoin (the active ingredient contained in Dilantin)


Genitourinary side effects have included Peyronie disease, male sexual dysfunction and, more rarely, priapism has been associated with phenytoin (the active ingredient contained in Dilantin) therapy.


Metabolic side effects associated with phenytoin (the active ingredient contained in Dilantin) therapy may include significantly reduced serum and red blood cell folate levels.


Ocular side effects including cataracts have been reported. Several human case reports and animal studies have suggested that phenytoin (the active ingredient contained in Dilantin) may predispose patients to the development of presenile cataracts. Chronic conjunctivitis has also been reported.

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