Phenytoin

Seizure Management

Phenytoin is an antiepileptic drug, also called an anticonvulsant. It is used to control certain types of seizures, including:

• Generalized tonic-clonic seizures: These involve a loss of consciousness and muscle contractions throughout the body.
• Complex partial seizures: These affect a specific area of the brain and may involve changes in awareness or behavior.

Surgical Use

Healthcare providers also use phenytoin to prevent or treat seizures that might occur during or after surgery on the brain or nervous system. It helps stabilize electrical activity in the brain during the recovery period.

Important Considerations

Phenytoin is not used for every type of seizure. It is typically not effective for absence seizures, which were previously called petit mal seizures.

Mechanism of Action

Phenytoin belongs to a class of medications called anticonvulsants. It works by stabilizing the electrical activity of nerve cells in the brain to prevent seizures from occurring or spreading.

Stabilizing Nerve Cells

Seizures are caused by sudden, abnormal, and excessive electrical discharges in the brain. Phenytoin helps manage this by:

• Limiting electrical spread: It helps prevent abnormal electrical signals from spreading to other parts of the brain, which can stop a localized seizure from becoming more severe.
• Regulating sodium levels: The medication affects the movement of sodium ions in and out of nerve cells. By slowing the flow of sodium, it makes the nerve cells less likely to fire excessively or become overexcited.

By keeping the brain's electrical signals within a normal range, phenytoin helps reduce the frequency and intensity of seizure episodes.

Common Side Effects

• Drowsiness, dizziness, or confusion
• Slurred speech or decreased coordination
• Nausea, vomiting, or constipation
• Headache
• Swelling, tenderness, or bleeding of the gums
• Increased hair growth on the face or body
• Coarsening of facial features

Serious Side Effects

Seek medical attention immediately for any of the following serious symptoms:

• Severe skin rash, hives, or blistering and peeling skin
• Fever, sore throat, or swollen lymph nodes
• Yellowing of the skin or eyes (jaundice)
• Unusual bruising or bleeding
• New or worsening depression, anxiety, or thoughts of self-harm
• Persistent bone or joint pain
• Severe stomach pain or loss of appetite

Serious Skin Reactions

Phenytoin can cause rare but life-threatening skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These reactions may be more common in individuals of certain Asian ancestries who carry a specific genetic marker (HLA-B*1502). Healthcare providers may recommend genetic testing before starting the medication.

Suicidal Thoughts and Behavior

Like other antiepileptic drugs, phenytoin may increase the risk of suicidal thoughts or actions. This can occur as early as one week after starting the medication. Changes in mood, worsening depression, or unusual behavior require immediate medical attention.

Hypersensitivity and DRESS

Some patients may experience a serious condition called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity. This condition can affect the liver, kidneys, or heart and may be fatal if not addressed early. Patients with a history of hypersensitivity to other anticonvulsants like carbamazepine or phenobarbital are at higher risk.

Liver and Blood Complications

Phenytoin can cause liver damage or significant changes in blood cell counts, such as low white blood cells or platelets. Regular blood tests are often necessary to monitor liver function and blood health during treatment. If signs of liver dysfunction occur, such as jaundice or dark urine, the medication may need to be discontinued.

Pregnancy and Fetal Risk

Taking phenytoin during pregnancy may increase the risk of birth defects, including craniofacial abnormalities and heart defects, a condition sometimes called fetal hydantoin syndrome. It may also cause life-threatening bleeding in newborns if not managed with vitamin K supplementation. Healthcare providers typically weigh the risks of seizures against the risks to the fetus.

Abrupt Withdrawal

Stopping phenytoin suddenly can lead to a rapid increase in seizure frequency or a life-threatening state of continuous seizures known as status epilepticus. Any changes to the dosage or discontinuation of the drug must be supervised by a healthcare professional and usually involves a gradual reduction in dose.

Other Precautions

• Bone Health: Long-term use may interfere with vitamin D metabolism, potentially leading to bone thinning (osteoporosis) or softening (osteomalacia).
• Drug Interactions: Phenytoin interacts with many other medications, which can change how well those drugs work or increase the risk of side effects. It is highly protein-bound, meaning other drugs can displace it and lead to toxicity.
• Lymph Node Changes: Phenytoin may cause swelling of the lymph nodes (lymphadenopathy), which requires medical evaluation to distinguish it from other conditions.

Pregnancy

Phenytoin is known to increase the risk of major birth defects, such as cleft lip, cleft palate, and heart malformations. These risks may be higher in women taking more than one anticonvulsant medication. Exposure in the womb can also lead to fetal hydantoin syndrome, which involves abnormalities of the face, limbs, and growth.

Taking phenytoin during pregnancy may cause bleeding problems in the newborn due to a decrease in blood-clotting factors. To help prevent this, healthcare providers may recommend vitamin K supplements for the mother during the final month of pregnancy and for the infant immediately after birth.

It is critical not to stop taking phenytoin suddenly if you become pregnant, as uncontrolled seizures can pose a serious threat to both the mother and the fetus. Patients are encouraged to discuss pregnancy planning and seizure management with their healthcare provider. Phenytoin may also make certain hormonal birth control methods less effective.

Breastfeeding

Phenytoin passes into breast milk in small concentrations. Because of the potential for side effects in the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the medicine to the mother. Mothers should consult their healthcare provider to weigh the benefits of breastfeeding against the potential risks to the baby.

Oral Formulations

Phenytoin is available in several oral forms to accommodate different dosing needs:

• Extended-release capsules: These contain phenytoin sodium and are designed to release the medication slowly into the bloodstream.
• Prompt-release capsules: These also contain phenytoin sodium but release the medication more quickly than extended-release versions.
• Chewable tablets: These contain phenytoin (acid) and are often used for patients who have difficulty swallowing capsules.
• Oral suspension: This is a liquid form of phenytoin (acid). It must be shaken thoroughly before each dose to ensure the medication is evenly mixed.

Injectable Formulations

Phenytoin is available as an injectable solution containing phenytoin sodium. This form is typically administered by a healthcare professional in a hospital or clinical setting, either as a slow intravenous (IV) injection or as an IV infusion.

Important Considerations

It is important to note that phenytoin sodium (found in capsules and injections) and phenytoin (found in chewable tablets and suspension) are not equivalent in strength. Because they are absorbed differently by the body, a healthcare provider may need to adjust the dose if a patient switches between different forms or brands of the medication.

FDA Approval and Indications

Phenytoin was first approved by the U.S. Food and Drug Administration (FDA) in 1939. It is indicated for the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures. It is also approved for the prevention and treatment of seizures occurring during or following neurosurgery.

Boxed Warning

The FDA has issued a boxed warning specifically for the intravenous (IV) administration of phenytoin. Rapid intravenous infusion is associated with severe cardiovascular reactions, including low blood pressure (hypotension) and heart rhythm disturbances (arrhythmias). To reduce these risks, the FDA requires that the rate of IV administration be strictly limited and that cardiac monitoring be performed during and after the infusion.

Safety Communications and Precautions

The FDA has issued safety communications regarding the risk of serious and potentially fatal dermatologic reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These risks are significantly higher in patients with the HLA-B*1502 genetic allele, which is more common in individuals of Asian descent. The FDA recommends considering genetic screening for at-risk populations before starting phenytoin therapy.

Like other antiepileptic drugs, phenytoin carries a general FDA-mandated warning regarding an increased risk of suicidal thoughts or behavior. Patients and caregivers are advised to monitor for any changes in mood, symptoms of depression, or unusual behavior while taking this medication.

Risks of Sudden Discontinuation

It is critical not to stop taking phenytoin or change your dosage without medical supervision. Abruptly ending treatment can lead to a significant increase in seizure frequency. The most serious risk is status epilepticus, a condition where seizures occur continuously or so frequently that the person does not regain consciousness between them.

Gradual Tapering

When phenytoin treatment needs to be discontinued, healthcare providers usually recommend a gradual reduction in dosage. This tapering process is designed to prevent the sudden onset of severe seizures. If you miss doses or are unable to take your medication, contact your doctor immediately to discuss how to safely manage your treatment.

Always follow your provider's specific instructions for lowering your dose to ensure your safety during the transition. If you experience an increase in seizures or new types of seizures while your dose is being adjusted, seek medical attention immediately.